BioMed Research International: Cardiology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Irrigated Tip Catheters for Radiofrequency Ablation in Ventricular Tachycardia Thu, 29 Jan 2015 09:04:45 +0000 Radiofrequency (RF) ablation with irrigated tip catheters decreases the likelihood of thrombus and char formation and enables the creation of larger lesions. Due to the potential dramatic consequences, the prevention of thromboembolic events is of particular importance for left-sided procedures. Although acute success rates of ventricular tachycardia (VT) ablation are satisfactory, recurrence rate is high. Apart from the progress of the underlying disease, reconduction and the lack of effective transmural lesions play a major role for VT recurrences. This paper reviews principles of lesion formation with radiofrequency and the effect of tip irrigation as well as recent advances in new technology. Potential areas of further development of catheter technology might be the improvement of mapping by better substrate definition and resolution, the introduction of bipolar and multipolar ablation techniques into clinical routine, and the use of alternative sources of energy. Andreas Müssigbrodt, Matthias Grothoff, Borislav Dinov, Jedrzej Kosiuk, Sergio Richter, Philipp Sommer, Ole A. Breithardt, Sascha Rolf, Andreas Bollmann, Arash Arya, and Gerhard Hindricks Copyright © 2015 Andreas Müssigbrodt et al. All rights reserved. Body Composition Indices and Predicted Cardiovascular Disease Risk Profile among Urban Dwellers in Malaysia Thu, 29 Jan 2015 07:15:35 +0000 Objectives. This study aims to compare various body composition indices and their association with a predicted cardiovascular disease (CVD) risk profile in an urban population in Kuala Lumpur, Malaysia. Methods. A cross-sectional survey was conducted in metropolitan Kuala Lumpur, Malaysia, in 2012. Households were selected using a simple random-sampling method, and adult members were invited for medical screening. The Framingham Risk Scoring algorithm was used to predict CVD risk, which was then analyzed in association with body composition measurements, including waist circumference, waist-hip ratio, waist-height ratio, body fat percentage, and body mass index. Results. Altogether, 882 individuals were included in our analyses. Indices that included waist-related measurements had the strongest association with CVD risk in both genders. After adjusting for demographic and socioeconomic variables, waist-related measurements retained the strongest correlations with predicted CVD risk in males. However, body mass index, waist-height ratio, and waist circumference had the strongest correlation with CVD risk in females. Conclusions. The waist-related indicators of abdominal obesity are important components of CVD risk profiles. As waist-related parameters can quickly and easily be measured, they should be routinely obtained in primary care settings and population health screens in order to assess future CVD risk profiles and design appropriate interventions. Tin Tin Su, Mohammadreza Amiri, Farizah Mohd Hairi, Nithiah Thangiah, Maznah Dahlui, and Hazreen Abdul Majid Copyright © 2015 Tin Tin Su et al. All rights reserved. Relationship between Sum of the Four Limbs’ Pulse Pressure and Brachial-Ankle Pulse Wave Velocity and Atherosclerosis Risk Factors in Chinese Adults Wed, 28 Jan 2015 08:18:32 +0000 The aim of the present study was to analyze the relationship between the sum of the four limbs’ pulse pressure (Sum-PP) and brachial-ankle pulse wave velocity (baPWV) and atherosclerosis risk factors and evaluate the feasibility of Sum-PP in diagnosing atherosclerosis systemically. For the purpose, a cross-sectional study was conducted on the basis of medical information of 20748 adults who had a health examination in our hospital. Both Sum-PP and baPWV exhibited significant variations among different human populations grouped by gender, smoking, drinking, and age. Interestingly, Sum-PP had similar varying tendency with baPWV in different populations. And further study in different populations showed that Sum-PP was significantly positively related to baPWV. We also investigated the relationship between Sum-PP, baPWV, and cardiovascular risk factors, respectively. We found that both Sum-PP and baPWV had significant positive correlation with atherosclerosis risk factors while both of them were negatively related to HDL-c. In addition, there was a significant close correlation between Sum-PP and baPWV in the whole population (, ). Thus, Sum-PP is closely related to baPWV and is of important value for clinical diagnosis of atherosclerosis. Yansong Zheng, Zongbin Li, Hua Shu, Minyan Liu, Zhilai Chen, and Jianhua Huang Copyright © 2015 Yansong Zheng et al. All rights reserved. Epicardial Adipose Tissue Reflects the Presence of Coronary Artery Disease: Comparison with Abdominal Visceral Adipose Tissue Tue, 27 Jan 2015 11:31:39 +0000 Accumulation of visceral adipose tissue is associated with a risk of coronary artery disease (CAD). The aim of this study was to examine whether different types of adipose tissue depot may play differential roles in the progression of CAD. Consecutive 174 patients who underwent both computed tomography (CT) and echocardiography were analyzed. Cardiac and abdominal CT scans were performed to measure epicardial and abdominal visceral adipose tissue (EAT and abdominal VAT, resp.). Out of 174 patients, 109 and 113 patients, respectively, presented coronary calcification (CC) and coronary atheromatous plaque (CP). The EAT and abdominal VAT areas were larger in patients with CP compared to those without it. Interestingly, the EAT area was larger in patients with CC compared to those without CC, whereas no difference was observed in the abdominal VAT area between patients with CC and those without. Multivariable logistic regression analysis revealed that the presence of echocardiographic EAT was an independent predictor of CP and CC, but the abdominal VAT area was not. These results suggest that EAT and abdominal VAT may play differential pathological roles in CAD. Given the importance of CC and CP, we should consider the precise assessment of CAD when echocardiographic EAT is detected. Masayoshi Oikawa, Takashi Owada, Hiroyuki Yamauchi, Tomofumi Misaka, Hirofumi Machii, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, and Yasuchika Takeishi Copyright © 2015 Masayoshi Oikawa et al. All rights reserved. Noninvasive Physiologic Assessment of Coronary Stenoses Using Cardiac CT Tue, 20 Jan 2015 12:27:27 +0000 Coronary CT angiography (CCTA) has become an important noninvasive imaging modality in the diagnosis of coronary artery disease (CAD). CCTA enables accurate evaluation of coronary artery stenosis. However, CCTA provides limited information on the physiological significance of stenotic lesions. A noninvasive “one-stop-shop” diagnostic test that can provide both anatomical significance and functional significance of stenotic lesions would be beneficial in the diagnosis and management of CAD. Recently, with the introduction of novel techniques, such as myocardial CT perfusion, CT-derived fractional flow reserve (), and transluminal attenuation gradient (TAG), CCTA has emerged as a noninvasive method for the assessment of both anatomy of coronary lesions and its physiological consequences during a single study. This review provides an overview of the current status of new CT techniques for the physiologic assessments of CAD. Lei Xu, Zhonghua Sun, and Zhanming Fan Copyright © 2015 Lei Xu et al. All rights reserved. Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients Thu, 15 Jan 2015 13:32:23 +0000 The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD) patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years) and 32 unstable CAD (72.03 ± 4.3 years) and 20 healthy subjects (71.7 ± 5.2 years), matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC) of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people. Md Sayed Ali Sheikh, Ke Xia, Fei Li, Xu Deng, Umme Salma, Hai Deng, Liu Wei Wei, Tian-Lun Yang, and Jun Peng Copyright © 2015 Md Sayed Ali Sheikh et al. All rights reserved. Influence of Two Common Polymorphisms in the EPHX1 Gene on Warfarin Maintenance Dosage: A Meta-Analysis Tue, 06 Jan 2015 06:32:02 +0000 We conducted a meta-analysis to investigate the influence of two common single nucleotide polymorphisms (SNPs) (rs2292566 G>A and rs4653436 A>G) in the EPHX1 gene on warfarin maintenance dosages. Relevant literatures were searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, TX, USA) was used for this meta-analysis. Standard mean difference and its corresponding 95% confidence interval (95% CI) were calculated. Seven studies met the inclusion criteria, including 2,063 warfarin-treated patients. Meta-analysis results illustrated that EPHX1 rs2292566 G>A polymorphism might be strongly correlated with a higher maintenance dose of warfarin. However, no interaction of EPHX1 rs4653436 A>G polymorphism with warfarin maintenance dosage was detected. A further subgroup analysis based on stratification by ethnicity indicated that EPHX1 rs2292566 G>A polymorphism was positively correlated with warfarin maintenance dosage among Caucasians, but not Asians. No associations were observed between EPHX1 rs4653436 A>G polymorphism warfarin maintenance dosage among both Caucasians and Asians. Our meta-analysis provides robust and unambiguous evidence that EPHX1 rs2292566 polymorphism may affect the maintenance dose of warfarin in Caucasians. Hong-Qiang Liu, Chang-Po Zhang, Chang-Zhen Zhang, Xiang-Chen Liu, and Zun-Jing Liu Copyright © 2015 Hong-Qiang Liu et al. All rights reserved. Long-Term Effects and Prognosis in Acute Heart Failure Treated with Tolvaptan: The AVCMA Trial Mon, 10 Nov 2014 10:48:22 +0000 Background. Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis. Methods and Results. One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups. Conclusions. We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide. Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi Suzuki, Shu-ichi Saitoh, Isao Kubota, and Yasuchika Takeishi Copyright © 2014 Satoshi Suzuki et al. All rights reserved. Genetic Identification and Risk Factor Analysis of Asymptomatic Bacterial Colonization on Cardiovascular Implantable Electronic Devices Sun, 02 Nov 2014 11:40:39 +0000 Asymptomatic bacterial colonization of cardiovascular implantable electronic devices (CIEDs) is widespread and increases the risk of clinical CIED infection. The aim of the study was to evaluate the incidence of bacterial colonization of generator pockets in patients without signs of infection and to analyze the relationship with clinical infection and risk factors. From June 2011 to December 2012, 78 patients underwent CIED replacement or upgrade. Exclusion criteria included a clinical diagnosis of CIED infection, bacteremia, or infective endocarditis. All patients were examined for evidence of bacterial 16S rDNA on the device and in the surrounding tissues. Infection cases were recorded during follow-up. The bacterial-positive rate was 38.5% (30 cases); the coagulase-negative Staphylococcus detection rate was the highest (9 cases, 11.5%). Positive bacterial DNA results were obtained from pocket tissue in 23.1% of patients (18 cases), and bacterial DNA was detected on the device in 29.5% of patients (23 cases). During follow-up (median 24.6 months), two patients (6.7%, 2/30) became symptomatic with the same species of microorganism, S. aureus and S. epidermidis. Multivariable logistic regression analysis found that the history of bacterial infection, use of antibiotics, application of antiplatelet drugs, replacement frequency, and renal insufficiency were independent risk factors for asymptomatic bacterial colonization. Xian-Ming Chu, Bing Li, Yi An, Xue-Bin Li, and Ji-Hong Guo Copyright © 2014 Xian-Ming Chu et al. All rights reserved. Genetic Diversity of SCN5A Gene and Its Possible Association with the Concealed Form of Brugada Syndrome Development in Polish Group of Patients Mon, 20 Oct 2014 09:14:39 +0000 Brugada Syndrome (BS) is an inherited channelopathy associated with a high incidence of sudden cardiac death. The paper presents the discovery of new genetic variants of SCN5A gene which might be associated with the development of a concealed form of Brugada Syndrome. The study involved a group of 59 patients (37 men) with suspected concealed form of Brugada Syndrome. Pharmacological provocation with intravenous ajmaline administration was performed. Six patients with positive test results were subjected to molecular analysis of SCN5A gene with MSSCP method. Additionally, MSSCP genotyping was performed for samples obtained from the family members with Brugada Syndrome, despite the fact that they had negative ajmaline challenge test results. Genetic examinations of the SCN5A gene at 6 positive patients showed 6 known polymorphisms, 8 new single nucleotide point (SNP) variants located at exons, and 12 new single nucleotide point variants located at introns. Among new SNPs localized in SCN5A gene exons three SNPs affected the protein sequence. Beata Uziębło-Życzkowska, Grzegorz Gielerak, Paweł Siedlecki, and Beata Pająk Copyright © 2014 Beata Uziębło-Życzkowska et al. All rights reserved. Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis Thu, 16 Oct 2014 13:01:01 +0000 Background. Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. Method. Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. Results. Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD = 1.36, 95%CI: 0.37–2.36, ). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD = 1.73, 95%CI: 0.20–3.26, ), but not in Asians (SMD = 1.04, 95%CI: −0.33–2.40, ). Conclusion. The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs. Ze-Lin Sun, Qi-Ying Xie, Gong-Liang Guo, Ke Ma, and Yuan-Yuan Huang Copyright © 2014 Ze-Lin Sun et al. All rights reserved. Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension: A Sensitive Tool for Detection of Subclinical LV Impairment Wed, 15 Oct 2014 07:32:52 +0000 Early diagnosis of cardiac alterations in hypertensive heart disease is still challenging. Since such patients might have depressed global LV systolic strain or strain rate when EF is still normal, speckle-tracking echocardiography (STE) and tissue-Doppler imaging (TDI) combined with stress echocardiography might improve early diagnosis of cardiac alterations. In this prospective study standard 2D Doppler echocardiography, STE, and TDI were performed at rest and during bicycle exercise in 92 consecutive patients—46 hypertensive subjects with normal ejection fraction and 46 healthy controls. STE and TDI were used to measure global peak systolic LV circumferential strain (CS), longitudinal strain (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was significantly higher in hypertensive patients at rest (100.8 mmHg SD 13.5 mmHg; ) and during physical exercise testing (124.2 mmHg SD 13.4 mmHg; ). Hypertensive patients had significantly reduced values of systolic CS (), LS (), and SR () at rest as well as during physical exercise—CS (), LS (), and SR (). Using STE and TDI, reduced LV systolic strain and strain rate consistent with early cardiac alterations can be detected in patients with arterial hypertension. These findings were evident at rest and markedly pronounced during exercise echocardiography. Kai O. Hensel, Andreas Jenke, and Roman Leischik Copyright © 2014 Kai O. Hensel et al. All rights reserved. The Prognostic Impact of High On-Treatment Platelet Reactivity with Aspirin or ADP Receptor Antagonists: Systematic Review and Meta-Analysis Mon, 13 Oct 2014 07:55:07 +0000 Objective. Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64–68) and 22.7% (22.4–27.8), of female gender. After a median follow-up of 1 year (0.1–1), cardiac adverse events occurred in 8.3% (3–11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], ). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89–1.22, 0%). Conclusions. After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed. Fabrizio D’Ascenzo, Umberto Barbero, Marta Bisi, Claudio Moretti, Pierluigi Omedè, Enrico Cerrato, Giorgio Quadri, Federico Conrotto, Giuseppe Biondi Zoccai, James J. DiNicolantonio, Mauro Gasparini, Sripal Bangalore, and Fiorenzo Gaita Copyright © 2014 Fabrizio D’Ascenzo et al. All rights reserved. Novel Study on N-Nitrosamines as Risk Factors of Cardiovascular Diseases Wed, 27 Aug 2014 00:00:00 +0000 Millions of people are exposed daily to N-nitrosamines from different environmental sources. The present study aims at investigating the role of N-nitrosamines in the alteration of homocysteine, lipid profile, oxidative stress, paraoxonase activity, antioxidant enzymes, and free radicals which are important risk factors for CVD. In addition, biomarkers of cardiovascular diseases such as creatine kinase MB activity (CK-MB) and lactate dehydrogenase (LDH) as well as protein expression of both glutathione peroxidase and glutathione S-transferase π isozyme were assayed after treatment of rats with 0.2 mg/kg body weight of N-nitrosodibutylamine (NDBA), N-nitrosoethylbutylamine (NEBA), N-nitrosobutylpropylamine (NBPA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosodiphenylamine (NDPA) as a daily dose for two weeks. LDL levels, paraoxonase activity, reduced glutathione levels, and glutathione reductase activities were increased, whereas HDL levels decreased after treatment of rats with most of N-nitrosamines compared to control group. Moreover, levels of free radicals and catalase activity increased, whereas protein expression of both glutathione peroxidase and glutathione S-transferase decreased after treatment of rats with some N-nitrosamines. The data showed that most N-nitrosamines increased CK-MB and LDH activities. It is concluded that N-nitrosamines increased levels of free radicals, and decreased the activity of antioxidant enzymes which may consequently increase the incidence of CVDs. Salah A. Sheweita, Heba A. El-Bendery, and Mostafa H. Mostafa Copyright © 2014 Salah A. Sheweita et al. All rights reserved. Evaluation of the Effect of Andrographolide on Atherosclerotic Rabbits Induced by Porphyromonas gingivalis Mon, 18 Aug 2014 07:00:58 +0000 Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg). We had investigated the effect of andrographolide (AND) on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2–5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg), and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels () and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3–G5) exhibited reductions in interleukins (IL-1β and IL-6) and C-reactive protein (CRP) as compared to atherogenicgroup (G2). The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3–G5) compared with atherogenicgroup (G2). Also, alpha-smooth muscle actin (α-SMA) staining decreased within the plaques of atherogenicgroup (G2), while it was increased in treated groups (G3–G5). Lastly, groups treated with AV and AND (G3–G5) showed significant reduction of CD36 expression () compared to atherogenicgroup (G2). These results substantially proved that AND contain antiatherogenic activity. Rami Al Batran, Fouad Al-Bayaty, Mazen M. Jamil Al-Obaidi, Saba F. Hussain, and Tengku Z. Mulok Copyright © 2014 Rami Al Batran et al. All rights reserved. Effects of β-Adrenoceptor Subtypes on Cardiac Function in Myocardial Infarction Rats Exposed to Fine Particulate Matter (PM2.5) Tue, 12 Aug 2014 08:39:53 +0000 The pathophysiological mechanisms of heart failure (HF) stems were mainly from longstanding overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Recent studies highlighted the potential benefits of β1-adrenoceptor (β1-AR) blocker combined with β2-adrenergic receptor (β2-AR) agonist in patients with HF. Long-term exposure to fine particulate air pollution, such as particulate matter ≤ 2.5 μm in diameter (PM2.5), has been found associated with acute myocardial infarction (AMI) which is the most common cause of congestive HF. In this study, we have investigated the effect of combined metoprolol and terbutaline on cardiac function in a rat model of AMI exposed to PM2.5. Our results demonstrated that short-term exposure to PM2.5 contributes to aggravate cardiac function in rats with myocardial infarction. The combined use of β1-AR blocker and β2-AR agonist is superior to β1-AR blocker alone for the treatment of AMI rats exposed to PM2.5. The combination of β1-AR blocker and β2-AR agonist may decrease the mortality of patients with myocardial infarction who have been exposed to PM2.5. Yuping Gao, Jiyuan Lv, Yuanyuan Lin, Xuewen Li, Lixia Wang, Yanping Yin, and Yan Liu Copyright © 2014 Yuping Gao et al. All rights reserved. Adiponectin Ameliorates Endotoxin-Induced Acute Cardiac Injury Sun, 10 Aug 2014 08:25:35 +0000 Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS-) induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10 mg/kg) was intraperitoneally injected into wild-type (WT) and adiponectin-knockout (APN-KO) mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV) systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF- and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN) improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF- and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction. Yoshio Watanabe, Rei Shibata, Noriyuki Ouchi, Takahiro Kambara, Koji Ohashi, Li Jie, Yoko Inoue, Toyoaki Murohara, and Kimihiro Komori Copyright © 2014 Yoshio Watanabe et al. All rights reserved. Coronary CT Angiography in the Quantitative Assessment of Coronary Plaques Tue, 05 Aug 2014 05:16:27 +0000 Coronary computed tomography angiography (CCTA) has been recently evaluated for its ability to assess coronary plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and patient clinical presentations may provide insight into the pathophysiology of coronary artery plaque, thus assisting identification of vulnerable plaques which are associated with the development of acute coronary syndrome. CCTA-generated 3D visualizations allow evaluation of both coronary lesions and lumen changes, which are considered to enhance the diagnostic performance of CCTA. The purpose of this review is to discuss the recent developments that have occurred in the field of CCTA with regard to its diagnostic accuracy in the quantitative assessment of coronary plaques, with a focus on the characterization of plaque components and identification of vulnerable plaques. Zhonghua Sun and Lei Xu Copyright © 2014 Zhonghua Sun and Lei Xu. All rights reserved. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart Thu, 24 Jul 2014 06:41:21 +0000 The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. Sarai Limon-Miranda, Diana G. Salazar-Enriquez, Jesus Muñiz, Mario V. Ramirez-Archila, Enrique A. Sanchez-Pastor, Felipa Andrade, Jose G. Soñanez-Organis, Edgar F. Moran-Palacio, and Adolfo Virgen-Ortiz Copyright © 2014 Sarai Limon-Miranda et al. All rights reserved. The Study of Fetal Rat Model of Intra-Amniotic Isoproterenol Injection Induced Heart Dysfunction and Phenotypic Switch of Contractile Proteins Sun, 20 Jul 2014 08:53:12 +0000 To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure. Yifei Li, Jie Fang, Yimin Hua, Chuan Wang, Dezhi Mu, and Kaiyu Zhou Copyright © 2014 Yifei Li et al. All rights reserved. Intra-QT Spectral Coherence as a Possible Noninvasive Marker of Sustained Ventricular Tachycardia Tue, 15 Jul 2014 12:55:40 +0000 Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the wave to the T wave peak () and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the -Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without ( versus , ). Although the responsible mechanism remains conjectural, the -Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias. Gianfranco Piccirillo, Federica Moscucci, Alessandro Persi, Daniele Di Barba, Maria Antonella Pappadà, Pietro Rossi, Raffaele Quaglione, Bich Lien Nguyen, Francesco Barillà, Matteo Casenghi, and Damiano Magrì Copyright © 2014 Gianfranco Piccirillo et al. All rights reserved. Cardiac Troponin T (TNNT2) Mutations in Chinese Dilated Cardiomyopathy Patients Mon, 07 Jul 2014 09:46:49 +0000 Background. Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. Although more than 40 genes have been reported to cause DCM, the role of genetic testing in clinical practice is not well defined. Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM. Therefore, the aim of the present study was to determine the genetic variations in TNNT2 and the associations of those variations with DCM in Chinese patients. Methods. An approximately 4 kb fragment of the TNNT2 gene was isolated from 103 DCM patients and 192 healthy controls and was analyzed by DNA sequence analysis for genetic variations. Results. A total of 6 TNNT2 mutations were identified in 99 patients, including a G321T missense mutation (Leu84Phe) and 5 novel intronic mutations. Alleles of two novel SNPs (c. CA, OR , 95% CI: , ; c. GA, OR , 95% CI: , ) and SNP rs3729843 (OR , 95% CI: ; ) were significantly correlated with DCM. Conclusions. These results suggest that the missense mutation (Leu84Phe) and two novel SNPs (c. CA, c. GA) in TNNT2 gene might be associated with DCM in the Chinese population. Xiaoping Li, Rong Luo, Haiyong Gu, Yun Deng, Xiaolei Xu, Xiushan Wu, and Wei Hua Copyright © 2014 Xiaoping Li et al. All rights reserved. Beneficial Effects of Testosterone Therapy on Functional Capacity, Cardiovascular Parameters, and Quality of Life in Patients with Congestive Heart Failure Sun, 06 Jul 2014 11:29:56 +0000 Background. According to the present evidences suggesting association between low testosterone level and prediction of reduced exercise capacity as well as poor clinical outcome in patients with heart failure, we sought to determine if testosterone therapy improves clinical and cardiovascular conditions as well as quality of life status in patients with stable chronic heart failure. Methods. A total of 50 male patients who suffered from congestive heart failure were recruited in a double-blind, placebo-controlled trial and randomized to receive an intramuscular (gluteal) long-acting androgen injection (1 mL of testosterone enanthate 250 mg/mL) once every four weeks for 12 weeks or receive intramuscular injections of saline (1 mL of 0.9% wt/vol NaCl) with the same protocol. Results. The changes in body weight, hemodynamic parameters, and left ventricular dimensional echocardiographic indices were all comparable between the two groups. Regarding changes in diastolic functional state and using Tei index, this parameter was significantly improved. Unlike the group received placebo, those who received testosterone had a significant increasing trend in 6-walk mean distance (6MWD) parameter within the study period (). The discrepancy in the trends of changes in 6MWD between study groups remained significant after adjusting baseline variables (mean square = 243.262, index = 4.402, and ). Conclusion. Our study strengthens insights into the beneficial role of testosterone in improvement of functional capacity and quality of life in heart failure patients. Ahmad Mirdamadi, Mohammad Garakyaraghi, Ali Pourmoghaddas, Alireza Bahmani, Hamideh Mahmoudi, and Mojgan Gharipour Copyright © 2014 Ahmad Mirdamadi et al. All rights reserved. Adenylyl Cyclase Signaling in the Developing Chick Heart: The Deranging Effect of Antiarrhythmic Drugs Mon, 23 Jun 2014 00:00:00 +0000 The adenylyl cyclase (AC) signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED) 8 significantly downregulated (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development. Lucie Hejnova, Klara Hahnova, Radka Kockova, Jarmila Svatunkova, David Sedmera, and Jiri Novotny Copyright © 2014 Lucie Hejnova et al. All rights reserved. Cardiac Proteomics Sun, 15 Jun 2014 07:08:35 +0000 Jatin G. Burniston, Anthony O. Gramolini, and R. John Solaro Copyright © 2014 Jatin G. Burniston et al. All rights reserved. The Effects of Beta-Glucan Rich Oat Bread on Serum Nitric Oxide and Vascular Endothelial Function in Patients with Hypercholesterolemia Thu, 12 Jun 2014 06:53:56 +0000 Introduction. Oats are high in soluble fibers and effective in reducing the risk of cardiovascular diseases (CVD). We assessed the effects of beta-glucan from oat bran on serum nitric oxide (NO) endothelial function in patients with hypercholesterolemia. Method. Sixty hypercholesterolemic patients were randomly divided to receive an experimental bread rich in beta-glucan from oat bran (intervention) or bread rich in wheat fiber (control) for four weeks. All subjects had the same diet for two-week baseline period and hypocaloric diet for four weeks of intervention. Serum NO concentration and flow-mediated dilation (FMD) were determined before and after the experiment. Results. Mean age of the participants was 51.1 ± 9.3 years and 65% () were female. After intervention, serum NO concentration increased by 50.2 ± 19.8 μmol/lit in the intervention group (), but no change was observed in the control group (17.5 ± 27.5 μmol/lit; ). No change of FMD was observed in the intervention (0.48 ± 0.78%; ) or in the control group (0.59 ± 0.92%; ). Conclusion. Consumption of oat bread for four weeks increases serum NO concentration but has no effect on FMD. Further studies are warranted in this regard. Faezeh Tabesh, Hamid Sanei, Mansour Jahangiri, Amir Momenizadeh, Elham Tabesh, Kiana Pourmohammadi, and Masoumeh Sadeghi Copyright © 2014 Faezeh Tabesh et al. All rights reserved. Biomechanical Evaluation of Ascending Aortic Aneurysms Wed, 04 Jun 2014 09:00:19 +0000 The biomechanical properties of ascending aortic aneurysms were investigated only in the last decade in a limited number of studies. Indeed, in recent years, there has been a growing interest in this field in order to identify new predictive parameters of risk of dissection, which may have clinical relevance. The researches performed so far have been conducted according to the methods used in the study of abdominal aortic aneurysms. In most cases, uniaxial or biaxial tensile tests were used, while in a smaller number of studies other methods, such as opening angle, bulge inflation, and inflation-extension tests, were used. However, parameters and protocols of these tests are at present very heterogeneous in the studies reported in the literature, and, therefore, the results are not comparable and are sometimes conflicting. The purpose of this review then thence to provide a comprehensive analysis of the experimental methodology for determination of biomechanical properties in the specific field of aneurysms of the ascending aorta to allow for better comparison and understanding of the results. Andrea Avanzini, Davide Battini, Lorenzo Bagozzi, and Gianluigi Bisleri Copyright © 2014 Andrea Avanzini et al. All rights reserved. Electrophysiological Studies in Patients with Pulmonary Hypertension: A Retrospective Investigation Mon, 26 May 2014 11:26:37 +0000 Few studies have investigated patients with pulmonary hypertension and arrhythmias. Data on electrophysiological studies in these patients are rare. In a retrospective dual-centre design, we analysed data from patients with indications for electrophysiological study. Fifty-five patients with pulmonary hypertension were included (Dana Point Classification: group 1: 14, group 2: 23, group 3: 4, group 4: 8, group 5: 2, and 4 patients with exercised-induced pulmonary hypertension). Clinical data, 6-minute walk distance, laboratory values, and echocardiography were collected/performed. Nonsustained ventricular tachycardia was the most frequent indication () for an electrophysiological study, followed by atrial flutter (). In summary 36 ablations were performed and 25 of them were successful (atrial flutter 12 of 14 and atrioventricular nodal reentrant tachycardia 4 of 4). Fluoroscopy time was 16 14.4 minutes. Electrophysiological studies in patients with pulmonary hypertension are feasible and safe. Ablation procedures are as effective in these patients as in non-PAH patients with atrial flutter and atrioventricular nodal reentrant tachycardia and should be performed likewise. The prognostic relevance of ventricular stimulations and inducible ventricular tachycardias in these patients is still unclear and requires further investigation. Dirk Bandorski, Jörn Schmitt, Claudia Kurzlechner, Damir Erkapic, Christian W. Hamm, Werner Seeger, Ardeschir Ghofrani, Reinhard Höltgen, and Henning Gall Copyright © 2014 Dirk Bandorski et al. All rights reserved. Percutaneous Extraction of Transvenous Permanent Pacemaker/Defibrillator Leads Mon, 26 May 2014 05:58:50 +0000 Background. Widespread use of cardiovascular implantable electronic devices has inevitably increased the need for lead revision/replacement. We report our experience in percutaneous extraction of transvenous permanent pacemaker/defibrillator leads. Methods. Thirty-six patients admitted to our centre from September 2005 through October 2012 for percutaneous lead extraction were included. Lead removal was attempted using Spectranetics traction-type system (Spectranetics Corp., Colorado, CO, USA) and VascoExtor countertraction-type system (Vascomed GmbH, Weil am Rhein, Germany). Results. Lead extraction was attempted in 59 leads from 36 patients (27 men), mean ± SD age years, with permanent pacemaker , defibrillator , or cardiac resynchronisation therapy with a mean ± SD implant duration of months. The indications for lead removal included pocket infection , endocarditis , and ventricular and atrial lead dysfunction . Traction device was used for 33 leads and countertraction device for 26 leads. Mean ± SD fluoroscopy time was minutes/lead for leads implanted <48 months and minutes/lead for leads implanted >48 months , . Complete procedural success rate was 91.7% and clinical procedural success rate was 100%, while lead procedural success rate was 95%. Conclusions. In conclusion, percutaneous extraction of transvenous permanent pacemaker/defibrillator leads using dedicated removal tools is both feasible and safe. Stylianos Paraskevaidis, Dimitrios Konstantinou, Vassilios Vassilikos, Efstratios Theofilogiannakos, Lilian Mantziari, Athanasia Megarisiotou, Ioannis Galitsianos, and Charalambos Karvounis Copyright © 2014 Stylianos Paraskevaidis et al. All rights reserved. Evaluation of Alexithymia, Somatosensory Sensitivity, and Health Anxiety Levels in Patients with Noncardiac Chest Pain Sun, 25 May 2014 11:21:37 +0000 Objective. Noncardiac chest pain (NCCP) is seen more frequently in young population and in these patients loss of function is evolving in social and professional areas. The aim of the study is to evaluate the levels of anxiety and somatic perception in patients with chest pain presenting to cardiology clinic. Methods. Fifty-one patients with noncardiac chest pain and 51 healthy controls were included in the study. All participants performed self-report based health anxiety inventory (HAI), somatosensory amplification scale (SAS), and Toronto alexithymia scale (TAS). Results. The patient group had significantly higher scores on the SAS, HAI-1, and HAI-T scales compared to controls (, , and , resp.). SAS, HAI-1, and HAI-T scores were significantly higher in female patients than male (, 0.036, and 0.039, resp.). There were significant differences in all TAS subscale scores between two groups. Patients, who had total TAS score more than 50, also presented higher levels of health anxiety (). Conclusions. Anxiety, somatic symptoms, and the exaggerated sense of bodily sensations are common in patients with NCCP. These patients unnecessarily occupy the cardiology outpatient clinics. These negative results can be eliminated when consultation-liaison psychiatry evaluates these patients in collaboration with cardiology departments. Selma Bozkurt Zincir, Murat Sunbul, Esra Aydin Sunbul, Bahar Dalkilic, Fatma Cengiz, Tarik Kivrak, and Erdal Durmus Copyright © 2014 Selma Bozkurt Zincir et al. All rights reserved. Forces Applied during Transvenous Implantable Cardioverter Defibrillator Lead Removal Wed, 21 May 2014 11:09:23 +0000 Methods. 17 physicians, experienced in transvenous lead removal, performed a lead extraction manoeuvre of an ICD lead on a torso phantom. They were advised to stop traction only when further traction would be considered as harmful to the patient or when—based on their experience—a change in the extraction strategy was indicated. Traction forces were recorded with a digital precision gauge. Results. Median traction forces on the endocardium were 10.9 N (range from 3.0 N to 24.7 N and interquartile range from 7.9 to 15.3). Forces applied to the proximal end were estimated to be 10% higher than those measured at the tip of the lead due to a friction loss. Conclusion. A traction force of around 11 N is typically exerted during standard transvenous extraction of ICD leads. A traction threshold for a safe procedure derived from a pool of experienced extractionists may be helpful for the development of required adequate simulator trainings. Carsten Lennerz, Herribert Pavaci, Christian Grebmer, Gesa von Olshausen, Verena Semmler, Alessandra Buiatti, Tilko Reents, Sonia Ammar, Isabel Deisenhofer, and Christof Kolb Copyright © 2014 Carsten Lennerz et al. All rights reserved. Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction Thu, 08 May 2014 08:13:33 +0000 Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival () or MACE (). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding. J. P. Howard, D. A. Jones, S. Gallagher, K. Rathod, S. Antoniou, P. Wright, C. Knight, A. Mathur, R. Weerackody, and A. Wragg Copyright © 2014 J. P. Howard et al. All rights reserved. Significance of Soluble Lectin-Like Oxidized LDL Receptor-1 Levels in Systemic and Coronary Circulation in Acute Coronary Syndrome Wed, 07 May 2014 13:12:43 +0000 Background. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) level is a novel biomarker for diagnosis of acute coronary syndrome (ACS); however, this level in the coronary circulation has yet to be examined. Methods. Twenty-seven consecutive patients with ACS and 40 patients with effort angina pectoris (EAP) undergoing percutaneous coronary intervention (PCI) had levels of soluble LOX-1 and LOX-1 index measured in paired blood samples from aorta (Ao) and coronary sinus (CS) just prior to the PCI. Results. We found positive correlations between soluble LOX-1 levels in the Ao and CS in both ACS and EAP patients (, for both). The soluble LOX-1 levels in the Ao and CS were higher in ACS than in EAP patients (, for both). The levels of soluble LOX-1 and LOX-1 index of the CS were significantly greater than those of the Ao in both ACS and EAP patients (, for both). Receiver operating characteristic curves for ACS detection demonstrated high sensitivity and specificity for the soluble LOX-1 and LOX-1 index with no differences between the Ao and CS. Conclusions. The present study showed that circulating soluble LOX-1 originates from coronary circulation and soluble LOX-1 and LOX-1 index are useful biomarkers for ACS. Tomofumi Misaka, Satoshi Suzuki, Nobuo Sakamoto, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Tatsuya Sawamura, Toshiyuki Ishibashi, and Yasuchika Takeishi Copyright © 2014 Tomofumi Misaka et al. All rights reserved. Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders Sun, 04 May 2014 15:12:02 +0000 We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS) on atrial electromechanical delay (AEMD) in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders. Mustafa Akçakoyun, Elnur Alizade, Recep Gündoğdu, Mustafa Bulut, Mehmet Mustafa Tabakcı, Göksel Açar, Anıl Avcı, Zeki Şimşek, Serdar Fidan, Serdar Demir, Ramazan Kargın, and Mehmet Yunus Emiroğlu Copyright © 2014 Mustafa Akçakoyun et al. All rights reserved. A Novel Stent Coated with Antibodies to Endoglin Inhibits Neointimal Formation of Porcine Coronary Arteries Sun, 04 May 2014 13:51:26 +0000 Endoglin/CD105 is an accessory protein of the transforming growth factor- receptor system that plays a critical role in proliferation of endothelial cells and neovasculature. Here, we aimed to assess the effect of novel stents coated with antibodies to endoglin (ENDs) on coronary neointima formation. Thirty ENDs, thirty sirolimus-eluting stents (SESs), and thirty bare metal stents (BMSs) were randomly assigned and placed in the coronary arteries in 30 juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed that after 7 days, there was no difference in the neointimal area and percent area stenosis in ENDs compared with SMSs or BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were markedly decreased than those in BMSs or SESs . Moreover, the percentage of reendothelialization was significantly higher in ENDs than that in SESs or BMSs at 7 and 14 days. The artery injury and the inflammation scores were similar in all groups at 7 and 14 days. In conclusion, our results demonstrated for the first time to our knowledge that endoglin antibody-coated stents can markedly reduce restenosis by enhancing reendothelialization in the porcine model and potentially offer a new approach to prevent restenosis. Song Cui, Jing-Hua Liu, Xian-Tao Song, Guo-Lin Ma, Ben-Jun Du, Shu-Zheng Lv, Li-Jun Meng, Quan-Sheng Gao, and Kefeng Li Copyright © 2014 Song Cui et al. All rights reserved. Endothelium in Diseased States Wed, 30 Apr 2014 12:22:27 +0000 Iveta Bernatova, Ramaroson Andriantsitohaina, Silvia M. Arribas, and Vladimir V. Matchkov Copyright © 2014 Iveta Bernatova et al. All rights reserved. Mas-Mediated Antioxidant Effects Restore the Functionality of Angiotensin Converting Enzyme 2-Angiotensin-(1–7)-Mas Axis in Diabetic Rat Carotid Tue, 29 Apr 2014 13:44:46 +0000 We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1–7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1–7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1–7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin-(1–7) were obtained in carotid from streptozotocin-induced diabetic rats. Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid endothelial cells. Carotid flow was also determined. We found that endothelial AT1-activated NAD(P)H oxidase-driven generation of superoxide and hydrogen peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1–7)-Mas axis functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide derived from superoxide dismutation inhibits ACE2 activity in generating angiotensin-(1–7) seemingly by activating , while superoxide inhibits the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1–7). Angiotensin-(1–7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1–7)-Mas axis functionality by triggering a positive feedback played by endothelial Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species. Mas-mediated antioxidant effects also restored diabetic rat carotid flow, pointing to the contribution of ACE2-angiotensin-(1–7)-Mas axis in maintaining carotid flow. Larissa Pernomian, Mayara Santos Gomes, Carolina Baraldi Araujo Restini, and Ana Maria de Oliveira Copyright © 2014 Larissa Pernomian et al. All rights reserved. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling Sun, 27 Apr 2014 11:25:44 +0000 Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined. Bernardo A. Petriz and Octavio L. Franco Copyright © 2014 Bernardo A. Petriz and Octavio L. Franco. All rights reserved. Building and Repairing the Heart: What Can We Learn from Embryonic Development? Thu, 17 Apr 2014 11:03:39 +0000 Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. Ana G. Freire, Tatiana P. Resende, and Perpétua Pinto-do-Ó Copyright © 2014 Ana G. Freire et al. All rights reserved. Factors Influencing Adaptation and Performance at Physical Exercise in Complex Congenital Heart Diseases after Surgical Repair Tue, 15 Apr 2014 13:19:22 +0000 In the last thirty years, steady progress in the diagnostic tools and care of subjects affected by congenital heart diseases (CHD) has resulted in a significant increase in their survival to adulthood, even for those affected by complex CHD. Based on these premises, a number of teenagers and adults affected by corrected (surgically or through interventional techniques) CHD ask to be allowed to undertake sporting activities, both at a recreational and competitive level. The purpose of this review is to examine the mechanisms influencing the adaption at physical exercise of patients suffering from complex CHD. The conclusion is that even if there are some modest risks with exercise, they should be seen in perspective, and the life-long benefits of regular exercise on general health, mood, and well-being should be emphasized. P. P. Bassareo, L. Saba, P. Solla, C. Barbanti, A. R. Marras, and G. Mercuro Copyright © 2014 P. P. Bassareo et al. All rights reserved. Neural Regulation of Cardiovascular Response to Exercise: Role of Central Command and Peripheral Afferents Wed, 09 Apr 2014 07:19:37 +0000 During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed. Antonio C. L. Nobrega, Donal O'Leary, Bruno Moreira Silva, Elisabetta Marongiu, Massimo F. Piepoli, and Antonio Crisafulli Copyright © 2014 Antonio C. L. Nobrega et al. All rights reserved. Improvement in Hemodynamic Responses to Metaboreflex Activation after One Year of Training in Spinal Cord Injured Humans Mon, 07 Apr 2014 14:02:57 +0000 Spinal cord injured (SCI) individuals show an altered hemodynamic response to metaboreflex activation due to a reduced capacity to vasoconstrict the venous and arterial vessels below the level of the lesion. Exercise training was found to enhance circulating catecholamines and to improve cardiac preload and venous tone in response to exercise in SCI subjects. Therefore, training would result in enhanced diastolic function and capacity to vasoconstrict circulation. The aim of this study was to test the hypothesis that one year of training improves hemodynamic response to metaboreflex activation in these subjects. Nine SCI individuals were enrolled and underwent a metaboreflex activation test at the beginning of the study (T0) and after one year of training (T1). Hemodynamics were assessed by impedance cardiography and echocardiography at both T0 and T1. Results show that there was an increment in cardiac output response due to metaboreflex activity at T1 as compared to T0 ( mL·min−1 versus  mL·min−1, ). Moreover, ventricular filling rate response was higher at T1 than at T0. Similarly, end-diastolic volume response was increased after training. We concluded that a period of training can successfully improve hemodynamic response to muscle metaboreflex activation in SCI subjects. Raffaele Milia, Silvana Roberto, Elisabetta Marongiu, Sergio Olla, Irene Sanna, Luca Angius, Pierpaolo Bassareo, Marco Pinna, Filippo Tocco, Alberto Concu, and Antonio Crisafulli Copyright © 2014 Raffaele Milia et al. All rights reserved. Human Pluripotent Stem Cell-Derived Cardiomyocytes as Research and Therapeutic Tools Wed, 02 Apr 2014 14:12:08 +0000 Human pluripotent stem cells (hPSCs), namely, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytes in vitro as well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Ivana Acimovic, Aleksandra Vilotic, Martin Pesl, Alain Lacampagne, Petr Dvorak, Vladimir Rotrekl, and Albano C. Meli Copyright © 2014 Ivana Acimovic et al. All rights reserved. The Chromosome 9p21 Variant Not Predicting Long-Term Cardiovascular Mortality in Chinese with Established Coronary Artery Disease: An Eleven-Year Follow-Up Study Wed, 02 Apr 2014 07:44:57 +0000 Introduction. We examined whether the variant at chromosome 9p21, rs4977574, was associated with long-term cardiovascular mortality in Han Chinese patients with coronary artery disease (CAD). Methodology. Subjects who underwent coronary angiography for chest pain were consecutively enrolled. Fasting blood samples were collected for laboratory and genotype assessments. The information was correlated with data collected from the national death database. Results. There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, in the dominant model; odds ratio = 1.36, in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, in the dominant model; hazard ratio = 1.05, in the recessive model). Conclusions. The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study. I-Te Lee, Mark O. Goodarzi, Wen-Jane Lee, Jerome I. Rotter, Yii-der Ida Chen, Kae-Woei Liang, Wen-Lieng Lee, and Wayne H.-H. Sheu Copyright © 2014 I-Te Lee et al. All rights reserved. Analysis of Pericardial Effusion from Idiopathic Pericarditis Patients by Two-Dimensional Gel Electrophoresis Wed, 02 Apr 2014 07:00:30 +0000 Pericardial fluid (PF) is often considered to be reflection of the serum by which information regarding the physiological status of the heart can be obtained. Some local and systemic disorders may perturb the balance between synthesis and discharge of PF and may cause its aberrant accumulation in the pericardial cavity as pericardial effusion (PE). PE may then lead to an increased intrapericardial pressure from which the heart function is undesirably affected. For some cases, the causes for the perturbance of fluid balance are well understood, but in some other cases, they are not apparent. It may, thus, be helpful to understand the molecular mechanisms behind this troublesome condition to elucidate a clinical approach for therapeutic uses. In this study, protein profiles of PEs from idiopathic pericarditis patients were analyzed. Control samples from patients undergoing elective cardiac surgery (ECS) were included for comparison. In addition to high abundant serum-originated proteins that may not hold significance for understanding the molecular mechanisms behind this disease, omentin-1 was identified and its level was higher for more than two-fold in PE of IP patients. Increased levels of omentin-1 in PE may open a way for understanding the molecular mechanisms behind idiopathic pericarditis (IP). Sadan Yavuz, Murat Kasap, Gurler Akpinar, Ersan Ozbudak, Dilek Ural, and Turan Berki Copyright © 2014 Sadan Yavuz et al. All rights reserved. The Endothelium, A Protagonist in the Pathophysiology of Critical Illness: Focus on Cellular Markers Tue, 01 Apr 2014 11:41:19 +0000 The endotheliumis key in the pathophysiology of numerous diseases as a result of its precarious function in the regulation of tissue homeostasis. Therefore, its clinical evaluation providing diagnostic and prognostic markers, as well as its role as a therapeutic target, is the focus of intense research in patientswith severe illnesses. In the critically ill with sepsis and acute brain injury, the endothelium has a cardinal function in the development of organ failure and secondary ischemia, respectively. Cellular markers of endothelial function such as endothelial progenitor cells (EPC) and endothelialmicroparticles (EMP) are gaining interest as biomarkers due to their accessibility, although the lack of standardization of EPC and EMP detection remains a drawback for their routine clinical use. In this paper we will review data available on EPC, as a general marker of endothelial repair, and EMP as an equivalent of damage in critical illnesses, in particular sepsis and acute brain injury. Their determination has resulted in new insights into endothelial dysfunction in the critically ill. It remains speculative whether their determination might guide therapy in these devastating acute disorders in the near future. Sabrina H. van Ierssel, Philippe G. Jorens, Emeline M. Van Craenenbroeck, and Viviane M. Conraads Copyright © 2014 Sabrina H. van Ierssel et al. All rights reserved. Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins Sun, 30 Mar 2014 07:15:23 +0000 Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200 mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5 min of limb ischemia followed by 5 min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. Safa Abdul-Ghani, Kate J. Heesom, Gianni D. Angelini, and M-Saadeh Suleiman Copyright © 2014 Safa Abdul-Ghani et al. All rights reserved. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity Wed, 26 Mar 2014 06:54:43 +0000 The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (), W/L (), and MCSA () and improved endothelium-dependent relaxation ( = versus = , ) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6 to 10−4 mol/l) for SHR-E with respect to WKY. SOSA () and nitrite () values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR. Ana Arnalich-Montiel, María Carmen González, Emilio Delgado-Baeza, María Jesús Delgado-Martos, Luis Condezo-Hoyos, Antonia Martos-Rodríguez, Pilar Rodríguez-Rodríguez, and Begoña Quintana-Villamandos Copyright © 2014 Ana Arnalich-Montiel et al. All rights reserved. The Association between the LPA Gene Polymorphism and Coronary Artery Disease in Chinese Han Population Tue, 25 Mar 2014 11:16:41 +0000 Lp(a) has been well known as an independent risk factor for coronary artery disease (CAD). The LPA gene, as it encodes apo(a) of the Lp(a) lipoprotein particle, was associated with increased risk of CAD. The purpose of this study was to analyze the relationship between the polymorphisms of LPA gene and CAD in Chinese Han population. Five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in the LPA gene were genotyped using Sequenom MassARRAY time-of-flight mass spectrometer (TOF) in 560 CAD patients as case group and 531 non-CAD subjects as control group. The numbers of these two groups were from Chinese Han ancestry. The results showed that allele () and genotype () of rs9364559 in the LPA gene was associated with CAD. The frequency of rs9364559 minor allele (G) in case group was obviously higher than that in control group. Results of haplotype analysis showed that 4 haplotypes which contained rs9364559-G were associated with increased risk of CAD in this population. This study explored rs9364559 in the LPA gene may be associated with the pathogenesis of CAD; and the risk of CAD might be higher in the population carrying 4 haplotypes of different blocks in the LPA gene. Zi-Kai Song, Hai-Di Wu, Hong-Yan Cao, and Ling Qin Copyright © 2014 Zi-Kai Song et al. All rights reserved. Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle Mon, 24 Mar 2014 08:09:14 +0000 Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18–29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, ). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction. Lisandra E. de Castro Brás, Hiroe Toba, Catalin F. Baicu, Michael R. Zile, Susan T. Weintraub, Merry L. Lindsey, and Amy D. Bradshaw Copyright © 2014 Lisandra E. de Castro Brás et al. All rights reserved. Proteomic Profiling of the Dystrophin-Deficient mdx Phenocopy of Dystrophinopathy-Associated Cardiomyopathy Thu, 20 Mar 2014 09:46:46 +0000 Cardiorespiratory complications are frequent symptoms of Duchenne muscular dystrophy, a neuromuscular disorder caused by primary abnormalities in the dystrophin gene. Loss of cardiac dystrophin initially leads to changes in dystrophin-associated glycoproteins and subsequently triggers secondarily sarcolemmal disintegration, fibre necrosis, fibrosis, fatty tissue replacement, and interstitial inflammation. This results in progressive cardiac disease, which is the cause of death in a considerable number of patients afflicted with X-linked muscular dystrophy. In order to better define the molecular pathogenesis of this type of cardiomyopathy, several studies have applied mass spectrometry-based proteomics to determine proteome-wide alterations in dystrophinopathy-associated cardiomyopathy. Proteomic studies included both gel-based and label-free mass spectrometric surveys of dystrophin-deficient heart muscle from the established mdx animal model of dystrophinopathy. Comparative cardiac proteomics revealed novel changes in proteins associated with mitochondrial energy metabolism, glycolysis, signaling, iron binding, antibody response, fibre contraction, basal lamina stabilisation, and cytoskeletal organisation. This review summarizes the importance of studying cardiomyopathy within the field of muscular dystrophy research, outlines key features of the mdx heart and its suitability as a model system for studying cardiac pathogenesis, and discusses the impact of recent proteomic findings for exploring molecular and cellular aspects of cardiac abnormalities in inherited muscular dystrophies. Ashling Holland and Kay Ohlendieck Copyright © 2014 Ashling Holland and Kay Ohlendieck. All rights reserved. Endothelial Function Increases after a 16-Week Diet and Exercise Intervention in Overweight and Obese Young Women Thu, 20 Mar 2014 08:11:17 +0000 Weight loss improves endothelial function in overweight individuals. The effects of weight loss through combined aerobic and resistance training and caloric restriction on in vivo vascular measures and blood markers associated with the regulation of endothelial function have not been comprehensively examined. Therefore, we investigated brachial artery endothelial function and potential regulatory blood markers in twenty overweight women (30.3 ± 2.0 years) who participated in 16 weeks of aerobic (5 d/wk) and resistance training (2 d/wk) (combined: ≥250 kcal/d) and caloric restriction (−500 kcal/d versus requirement). Resting brachial artery flow mediated dilation (FMD) and circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) were assessed at baseline and following the intervention. Relative and absolute FMD increased (before: 4.0 ± 0.5% versus after: 6.9 ± 0.6%, and before: 0.14 ± 0.02 mm versus after: 0.23 ± 0.02 mm, , resp.), while body mass decreased (before: 86.9 ± 2.4 kg versus after: 81.1 ± 2.4 kg, following the intervention. There were no changes in either blood marker (IL-6: before: 1.5 ± 0.2 pg/mL versus after: 1.5 ± 0.1 pg/mL, and ET-1: before: 0.55 ± 0.05 pg/mL versus after: 0.59 ± 0.09 pg/mL, ). 16 weeks of combined aerobic/resistance training and diet-induced weight loss improved endothelial function in overweight and obese young women, but this increase was not associated with changes in blood markers of vasoconstriction or inflammation. Lisa M. Cotie, Andrea R. Josse, Stuart M. Phillips, and Maureen J. MacDonald Copyright © 2014 Lisa M. Cotie et al. All rights reserved. Age-Related Alterations in Endothelial Function of Femoral Artery in Young SHR and WKY Rats Thu, 20 Mar 2014 07:49:43 +0000 The present study was designed to evaluate the effects of vascular aging in juvenescence on endothelial function in femoral arteries and to assess differences between normotensive and hypertensive rats. The aim of the study was to determine if age affected nitric oxide- (NO-) mediated relaxations in normotensive and hypertensive rats. Juvenile (7-week-old) and young adult (22-week-old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in this study. Femoral artery (FA) reactivity was determined by wire myograph and NO synthase activity by conversion of [3H]-L-arginine. During juvenescence systolic blood pressure (tail-cuff) increased significantly only in SHR, while NO synthesis decreased significantly in both strains. Endothelium-dependent relaxations to acetylcholine were reduced in the FA of SHR compared to age-matched WKY at both ages, yet these parameters were unchanged in adult rats compared with juvenile animals. The NO-dependent component of vasorelaxation was markedly reduced, whereas the NO-independent component was increased in adult compared to juvenile rats in both strains. The endothelial dysfunction in SHR at both ages was associated with reduction of NO-independent mechanisms. In conclusion, aging in early periods of life was associated with reduction of vascular NO production and bioavailability in both strains investigated. This reduction was however fully compensated by accentuation of NO-independent mechanisms. Angelika Puzserova, Veronika Ilovska, Peter Balis, Peter Slezak, and Iveta Bernatova Copyright © 2014 Angelika Puzserova et al. All rights reserved. Association of P2Y12 Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients Tue, 18 Mar 2014 11:32:12 +0000 Background. Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR). Methods. The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR. Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, ; CpG2, ) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients () and in subgroup of Albumin < 35 (). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR. Conclusions. The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR. Jia Su, Xiaojing Li, Qinglin Yu, Yahui Liu, Yaqing Wang, Haojun Song, Hanbin Cui, Weiping Du, Xiaohong Fei, Junsong Liu, Shaoyi Lin, Jian Wang, Wenyuan Zheng, Jinyan Zhong, Lulu Zhang, Maoqing Tong, Jin Xu, and Xiaomin Chen Copyright © 2014 Jia Su et al. All rights reserved. Recent Insights in the Paracrine Modulation of Cardiomyocyte Contractility by Cardiac Endothelial Cells Thu, 13 Mar 2014 16:17:58 +0000 The cardiac endothelium is formed by a continuous monolayer of cells that line the cavity of the heart (endocardial endothelial cells (EECs)) and the luminal surface of the myocardial blood vessels (intramyocardial capillary endothelial cells (IMCEs)). EECs and IMCEs can exercise substantial control over the contractility of cardiomyocytes by releasing various factors such as nitric oxide (NO) via a constitutive endothelial NO-synthase (eNOS), endothelin-1, prostaglandins, angiotensin II, peptide growth factors, and neuregulin-1. The purpose of the present paper is actually to shortly review recent new information concerning cardiomyocytes as effectors of endothelium paracrine signaling, focusing particularly on contractile function. The modes of action and the regulatory paracrine role of the main mediators delivered by cardiac endothelial cells upon cardiac contractility identified in cardiomyocytes are complex and not fully described. Thus, careful evaluation of new therapeutic approaches is required targeting important physiological signaling pathways, some of which have been until recently considered as deleterious, like reactive oxygen species. Future works in the field of cardiac endothelial cells and cardiac function will help to better understand the implication of these mediators in cardiac physiopathology. Jacques Noireaud and Ramaroson Andriantsitohaina Copyright © 2014 Jacques Noireaud and Ramaroson Andriantsitohaina. All rights reserved. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence? Thu, 13 Mar 2014 10:02:58 +0000 Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models. Iveta Bernatova Copyright © 2014 Iveta Bernatova. All rights reserved. Comparison of the Ventricle Muscle Proteome between Patients with Rheumatic Heart Disease and Controls with Mitral Valve Prolapse: HSP 60 May Be a Specific Protein in RHD Wed, 12 Mar 2014 08:05:44 +0000 Objective. Rheumatic heart disease (RHD) is a serious autoimmune heart disease. The present study was aimed at identifying the differentially expressed proteins between patients with RHD and controls with mitral valve prolapse. Methods. Nine patients with RHD and nine controls with mitral valve prolapsed were enrolled for this study. Two-dimensional difference in-gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were performed. Results. A total of 39 protein spots with differential expressions were identified between the two groups (, Average Ratio > 1.2 or Average Ratio < −1.2) and four upregulated proteins (including heat shock protein 60 (HSP 60), desmin, PDZ and LIM domain protein 1, and proteasome subunit alpha type-1) and three downregulated proteins (including tropomyosin alpha-1 chain, malate dehydrogenase, and chaperone activity of bc1 complex homolog) were determined. Conclusion. These seven proteins, especially HSP 60, may serve as potential biomarkers for the diagnosis of RHD and provide evidence to explain the mechanisms of this complex disease in the future. Dawei Zheng, Limin Xu, Lebo Sun, Qiang Feng, Zishan Wang, Guofeng Shao, and Yiming Ni Copyright © 2014 Dawei Zheng et al. All rights reserved. Genotype-Related Effect of Crowding Stress on Blood Pressure and Vascular Function in Young Female Rats Wed, 05 Mar 2014 13:14:10 +0000 This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone and accelerated BP ( versus basal) only in BHR. NO production and superoxide concentration were significantly higher in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh)-induced relaxation in the femoral artery was reduced in control SHR versus WKY and BHR, and stress did not affect it significantly in any genotype. The attenuation of ACh-induced relaxation in SHR versus WKY was associated with reduction of its NO-independent component. Crowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function. Peter Slezak, Angelika Puzserova, Peter Balis, Natalia Sestakova, Miroslava Majzunova, Ima Dovinova, Michal Kluknavsky, and Iveta Bernatova Copyright © 2014 Peter Slezak et al. All rights reserved. Nitric Oxide, Oxidative Stress, and Interplay in Diabetic Endothelial Dysfunction Wed, 05 Mar 2014 07:06:30 +0000 Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, protein. Alessandra Magenta, Simona Greco, Maurizio C. Capogrossi, Carlo Gaetano, and Fabio Martelli Copyright © 2014 Alessandra Magenta et al. All rights reserved. Brachial Artery Endothelial Responses during Early Recovery from an Exercise Bout in Patients with Coronary Artery Disease Mon, 03 Mar 2014 16:48:19 +0000 This study examined the acute endothelial responses to an exercise bout in coronary artery disease (CAD) patients. Nineteen males with CAD ( years) were assessed at rest and 15 minutes following a submaximal exercise bout (recovery). Brachial artery endothelial-dependent function was assessed using flow-mediated dilation (FMD). Brachial artery diameters and velocities were measured using Duplex ultrasound at baseline, and for 3 minutes following a 5-minute ischemic period. Endothelial-independent function was assessed using a 0.4 mg dose of nitroglycerin (NTG). FMD responses were unchanged from rest to recovery; however, there were 2 types of responses: negative and positive FMD responders. Post-hoc analysis revealed that positive responders had lower resting FMD compared to negative responders ( versus , ). NTG-mediated dilation was reduced in recovery ( versus , for rest versus recovery). In conclusion, acute endothelial-dependent responses to submaximal exercise are affected by the degree of resting endothelial dysfunction. The observation of attenuated NTG-mediated dilation during recovery is novel and warrants the investigation of possible mechanisms and clinical significance. Furthermore, it highlights the necessity of both endothelial-dependent and endothelial-independent assessments when evaluating endothelial function changes with an intervention. Katharine D. Currie, Robert S. McKelvie, and Maureen J. MacDonald Copyright © 2014 Katharine D. Currie et al. All rights reserved. The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke Thu, 27 Feb 2014 07:05:20 +0000 Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke. Cheng-I. Cheng, Yu-Chun Lin, Tzu-Hsien Tsai, Hung-Sheng Lin, Chia-Wei Liou, Wen-Neng Chang, Cheng-Hsien Lu, Chun-Man Yuen, and Hon-Kan Yip Copyright © 2014 Cheng-I. Cheng et al. All rights reserved. Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention Wed, 26 Feb 2014 15:39:03 +0000 The endothelium, which forms the inner cellular lining of blood vessels and lymphatics, is a highly metabolically active organ that is involved in many physiopathological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion, and trafficking and inflammation. In this review, we summarized and described the following: (i) endothelial cell function in physiological conditions and (ii) endothelial cell activation and dysfunction in the main cardiovascular diseases (such as atherosclerosis, and hypertension) and to diabetes, cigarette smoking, and aging physiological process. Finally, we presented the currently available evidence that supports the beneficial effects of physical activity and various dietary compounds on endothelial functions. Gaia Favero, Corrado Paganelli, Barbara Buffoli, Luigi Fabrizio Rodella, and Rita Rezzani Copyright © 2014 Gaia Favero et al. All rights reserved. Nitric Oxide and Superoxide Anion Balance in Rats Exposed to Chronic and Long Term Intermittent Hypoxia Wed, 26 Feb 2014 06:45:01 +0000 Work at high altitude in shifts exposes humans to a new form of chronic intermittent hypoxia, with still unknown health consequences. We have established a rat model resembling this situation, which develops a milder form of right ventricular hypertrophy and pulmonary artery remodelling compared to continuous chronic exposure. We aimed to compare the alterations in pulmonary artery nitric oxide (NO) availability induced by these forms of hypoxia and the mechanisms implicated. Rats were exposed for 46 days to normoxia or hypobaric hypoxia, either continuous (CH) or intermittent (2 day shifts, CIH2x2), and assessed: NO and superoxide anion availability (fluorescent indicators and confocal microscopy); expression of phosphorylated endothelial NO synthase (eNOS), NADPH-oxidase (p22phox), and 3-nitrotyrosine (western blotting); and NADPH-oxidase location (immunohistochemistry). Compared to normoxia, (1) NO availability was reduced and superoxide anion was increased in both hypoxic groups, with a larger effect in CH, (2) eNOS expression was only reduced in CH, (3) NADPH-oxidase was similarly increased in both hypoxic groups, and (4) 3-nitrotyrosine was increased to a larger extent in CH. In conclusion, intermittent hypoxia reduces NO availability through superoxide anion destruction, without reducing its synthesis, while continuous hypoxia affects both, producing larger nitrosative damage which could be related to the more severe cardiovascular alterations. Patricia Siques, Ángel Luis López de Pablo, Julio Brito, Silvia M. Arribas, Karen Flores, Karem Arriaza, Nelson Naveas, M. Carmen González, Alexander Hoorntje, Fabiola León-Velarde, and M. Rosario López Copyright © 2014 Patricia Siques et al. All rights reserved. The Endothelial ADMA/NO Pathway in Hypoxia-Related Chronic Respiratory Diseases Tue, 25 Feb 2014 07:34:03 +0000 Since its discovery, many adhere to the view that asymmetric dimethylarginine (ADMA), as an inhibitor of the synthesis of nitric oxide (NO), contributes to the pathogenesis of various diseases. Particularly, this is evident in disease of the cardiovascular system, in which endothelial dysfunction results in an imbalance between vasoconstriction and vasodilatation. Even if increased ADMA concentrations are closely related to an endothelial dysfunction, several studies pointed to a potential beneficial effect of ADMA, mainly in the context of angioproliferative disease such as cancer and fibrosis. Antiproliferative properties of ADMA independent of NO have been identified in this context. In particular, the regulation of ADMA by its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) is the object of many studies. DDAH is discussed as a promising therapeutic target for the indirect regulation of NO. In hypoxia-related chronic respiratory diseases, this controversy discussion of ADMA and DDAH is particularly evident and is therefore subject of this review. Nicole Lüneburg, Lars Harbaum, and Jan K. Hennigs Copyright © 2014 Nicole Lüneburg et al. All rights reserved. Contribution of Ca2+-Dependent Cl− Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing Sun, 23 Feb 2014 13:38:02 +0000 The activation of Ca2+-dependent Cl− channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca2+ entry. Hypertension and ageing are associated with altered Ca2+ handling including possible activation of Ca2+-dependent Cl− channels. Our study was aimed to determine Ca2+-dependent Cl− channels contribution to norepinephrine-induced contraction during hypertension and ageing. Norepinephrine-induced concentration-response curves of femoral arteries from 6- and 12-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were recorded using wire myograph. Pretreatment with Ca2+-dependent Cl- channel inhibitor indanyloxyacetic acid 94 [R(+)-IAA-94](IAA) attenuated norepinephrine-induced contraction in all groups, but relatively more in WKY than SHR arteries. The attenuation of norepinephrine-induced contraction after Ca2+-dependent Cl− channels blockade was partially reduced in 12-month-old WKY rats, but substantially diminished in 12-month-old SHR. IAA effect was enhanced after NO synthase inhibition but decreased by ageing. In 20-month-old WKY rats norepinephrine-induced contraction was not affected by IAA but was almost abolished after cyclooxygenase inhibition by indomethacin or niflumic acid. In conclusion, contribution of Ca2+-dependent Cl− channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca2+-dependent Cl− channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism. Silvia Liskova, Miriam Petrova, Petr Karen, Michal Behuliak, and Josef Zicha Copyright © 2014 Silvia Liskova et al. All rights reserved. Endothelial Function in a Mouse Model of Myeloperoxidase Deficiency Sun, 23 Feb 2014 00:00:00 +0000 Myeloperoxidase (MPO) activity is suggested to reduce the function of vascular nitric oxide, thereby contributing to endothelial dysfunction, although data in rodents are inconclusive. We examined vascular contractile and relaxant responses in MPO-deficient () and wild-type mice to investigate the role for myeloperoxidase in the development of endothelial dysfunction. Carotid and saphenous arteries were taken from 8-month-old mice and studied in a myograph. Responses of carotid arteries to phenylephrine, high potassium, or acetylcholine (Ach) were statistically not different from controls. Treatment with lipopolysaccharide (LPS; to enhance endothelial dysfunction) reduced responses to Ach in but did not affect responses in wild-type. In response to high concentrations of Ach, carotid arteries responded with transient contractions, which were not different between the groups and not affected by LPS treatment. Saphenous arteries from had smaller normalized diameters and developed less contractile force. Vessels from were less sensitive to Ach than controls. These data suggest that mature MPO-deficient mice do not show enhanced endothelial function compared to wild-type mice, even when provoked with LPS treatment. The EDHF response appears to be reduced in MPO deficiency. Veronika Golubinskaya, Ulla Brandt-Eliasson, Li-Ming Gan, Martin Kjerrulf, and Holger Nilsson Copyright © 2014 Veronika Golubinskaya et al. All rights reserved. GCK Gene-Body Hypomethylation Is Associated with the Risk of Coronary Heart Disease Mon, 17 Feb 2014 09:15:24 +0000 Objectives. Glucokinase encoded by GCK is a key enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Variants of GCK gene were shown to be associated with type 2 diabetes (T2D) and coronary heart disease (CHD). The goal of this study was to investigate the contribution of GCK gene-body methylation to the risk of CHD. Design and Methods. 36 patients (18 males and 18 females) and 36 age- and sex-matched controls were collected for the current methylation research. DNA methylation level of the CpG island (CGI) region on the GCK gene-body was measured through the sodium bisulfite DNA conversion and pyrosequencing technology. Results. Our results indicated that CHD cases have a much lower methylation level (49.77 ± 6.43%) compared with controls (54.47 ± 7.65%, ). In addition, GCK gene-body methylation was found to be positively associated with aging in controls (, ). Conclusions. Our study indicated that the hypomethylation of GCK gene-body was significantly associated with the risk of CHD. Aging correlates with an elevation of GCK methylation in healthy controls. Limin Xu, Dawei Zheng, Lingyan Wang, Danjie Jiang, Haibo Liu, Leiting Xu, Qi Liao, Lina Zhang, Panpan Liu, Xinbao Shi, Zhaoyang Wang, Lebo Sun, Qingyun Zhou, Ni Li, Yi Huang, Yanping Le, Meng Ye, Guofeng Shao, and Shiwei Duan Copyright © 2014 Limin Xu et al. All rights reserved. Shear Stress, Energy Losses, and Costs: A Resolved Dilemma of Pulsatile Cardiac Assist Devices Wed, 08 Jan 2014 09:09:52 +0000 Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device’s prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients. Sayed Nour, Jia Liu, Gang Dai, Daniel Carbognani, Daya Yang, Guifu Wu, Qinmei Wang, and Juan Carlos Chachques Copyright © 2014 Sayed Nour et al. All rights reserved. The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia Mon, 06 Jan 2014 12:29:49 +0000 Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD. Yuri M. Klyachkin, Anush V. Karapetyan, Mariusz Z. Ratajczak, and Ahmed Abdel-Latif Copyright © 2014 Yuri M. Klyachkin et al. All rights reserved. Peripheral Arterial Stiffness Is Independently Associated with a Rapid Decline in Estimated Glomerular Filtration Rate in Patients with Type 2 Diabetes Sun, 29 Dec 2013 13:15:08 +0000 Introduction. Diabetes and its vascular complications are main noncommunicable chronic diseases and major global health issues. Peripheral arterial disease (PAD) is highly prevalent in diabetes with nephropathy. We evaluated the associations of variables of arterial stiffness and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. Materials and Methods. A total of 577 type 2 diabetic patients (mea: age, years) were enrolled. A rapid decline in eGFR was defined as progressively lower eGFR detected at both the 6- and 12-month follow-up visits, plus a reduction in eGFR more than 3 mLmin−1per 1.73 m2 per year. Results. Higher glycated hemoglobin (HbA1c), systolic blood pressure (SBP), pulse pressure (PP), and brachial-ankle pulse wave velocity (ba-PWV) at baseline were independently associated with a rapid decline in eGFR. The adjusted odds ratios (95% confidence intervals) for a rapid decline in eGFR for ba-PWV, SBP, and PP were 1.072 (1.011–1.136), 1.014 (1.004–1.025), and 1.025 (1.008–1.041), respectively, after adjustment for gender, age, body mass index, smoking, HbA1c, and baseline eGFR in separated models. Conclusions. Ba-PWV may serve as a simple and noninvasive predictor of rapid renal function progression in type 2 diabetic patients. Yi-Jing Sheen, Jiann-Liang Lin, Tsai-Chung Li, Cho-Tsan Bau, and Wayne Huey-Herng Sheu Copyright © 2013 Yi-Jing Sheen et al. All rights reserved. Interval and Continuous Exercise Training Produce Similar Increases in Skeletal Muscle and Left Ventricle Microvascular Density in Rats Tue, 26 Nov 2013 15:37:49 +0000 Interval training (IT), consisting of alternated periods of high and low intensity exercise, has been proposed as a strategy to induce more marked biological adaptations than continuous exercise training (CT). The purpose of this study was to assess the effects of IT and CT with equivalent total energy expenditure on capillary skeletal and cardiac muscles in rats. Wistar rats ran on a treadmill for 30 min per day with no slope (0%), 4 times/week for 13 weeks. CT has constant load of 70% max; IT has cycles of 90% max for 1 min followed by 1 min at 50% max. CT and IT increased endurance and muscle oxidative capacity and attenuated body weight gain to a similar extent (). In addition, CT and IT similarly increased functional capillary density of skeletal muscle (CT: %; IT: %) and the capillary-to-fiber ratio in skeletal muscle (CT: %; IT: %) and in the left ventricle (CT: %; IT: %). In conclusion, at equivalent total work volumes, interval exercise training induced similar functional and structural alterations in the microcirculation of skeletal muscle and myocardium in healthy rats compared to continuous exercise training. Flávio Pereira, Roger de Moraes, Eduardo Tibiriçá, and Antonio C. L. Nóbrega Copyright © 2013 Flávio Pereira et al. All rights reserved. Is the Blood Pressure Paradox Observed in All Heart Failure Patients? Mon, 25 Nov 2013 11:11:48 +0000 Background. Heart failure (HF) patients with higher systolic blood pressure (SBP) survive longer. Diabetes mellitus (DM) is a frequent comorbidity in HF. We evaluated the prognostic significance of low SBP according to DM in acute HF. Methods. We prospectively recruited 589 patients admitted with acute HF. DM was defined according to the 2011 American Diabetes Association recommendations. Patients were followed for 6 months and HF-death was the endpoint. A multivariate Cox-regression model was used to assess the prognostic impact of SBP. A stratified analysis according to DM was performed. Results. Median patients’ age was 79 years and DM was present in 50.8%. Ischemic aetiology HF and hypertension history were more common in diabetics. Diabetic patients had worse renal function and lower total cholesterol and were more often discharged with antiplatelet therapy and statin. During followup, 89 patients died due to HF. The multivariate-adjusted HR for the 6-month HF death in non-diabetic patients with an admission SBP < 115 mmHg (1st quartile) was 2.94 (95% CI: 1.49–5.79), while lower admission SBP was not associated with HF mortality in diabetics. Conclusions. The blood pressure paradox in HF is only observed in non-diabetic HF patients. Diabetic patients seem to be a particular subgroup of HF patients. F. M. Cunha, P. Lourenço, M. Couto, P. Tavares, S. Silva, J. T. Guimarães, and P. Bettencourt Copyright © 2013 F. M. Cunha et al. All rights reserved. Effects of DL-Homocysteine Thiolactone on Cardiac Contractility, Coronary Flow, and Oxidative Stress Markers in the Isolated Rat Heart: The Role of Different Gasotransmitters Sun, 24 Nov 2013 10:11:02 +0000 Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured: dp/dt max, dp/dt min, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2, , and H2O2 concentrations. The administration of DL-Hcy TLHC alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF, , H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increased dp/dt max but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease in dp/dt max, SLVP, HR, CF, and TBARS. Vladimir Zivkovic, Vladimir Jakovljevic, Olga Pechanova, Ivan Srejovic, Jovana Joksimovic, Dragica Selakovic, Nevena Barudzic, and Dragan M. Djuric Copyright © 2013 Vladimir Zivkovic et al. All rights reserved. Association of CILP2 and ACE Gene Polymorphisms with Cardiovascular Risk Factors in Slovak Midlife Women Wed, 20 Nov 2013 14:45:38 +0000 The aim of this study is to assess the association of two polymorphisms, the cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical parameters related to the development of cardiovascular disease. The entire study sample comprised 341 women ranging in age from 39 to 65 years. The CILP2 genotypes were determined by PCR-RFLP and the ACE genotypes by PCR. The Bonferroni pairwise comparisons showed the effect of the CILP2 genotype on high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to-HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (). Here, higher mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid parameters were registered in the GT/TT genotype carriers than in GG carriers. Statistically significant association was identified between the ACE genotype and the following parameters: TC, LDL-C, and non-HDL-C (). The II genotype can lower serum level of TC (), LDL-C (), and non-HDL-C levels. The results of this study suggest that the minor T allele of CILP2 gene and I allele of ACE gene have a protective effect against elevated serum lipid and lipoprotein levels. Lenka Luptáková, Dominika Benčová, Daniela Siváková, and Marta Cvíčelová Copyright © 2013 Lenka Luptáková et al. All rights reserved. Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells Sun, 10 Nov 2013 09:56:30 +0000 IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology. Piera D’Elia, Vittoria Ionta, Isotta Chimenti, Francesco Angelini, Fabio Miraldi, Alessandro Pala, Elisa Messina, and Alessandro Giacomello Copyright © 2013 Piera D’Elia et al. All rights reserved. Gsk-3β Inhibitors Mimic the Cardioprotection Mediated by Ischemic Pre- and Postconditioning in Hypertensive Rats Wed, 30 Oct 2013 14:07:15 +0000 The aim of this study was to examine the effects of GSK-3β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl) or indirubin-3′-monoxime,5-iodo-(IMI) as GSK-3β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3β/VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3β/VDAC interaction is a crucial event. Luisa F. González Arbeláez, Ignacio A. Pérez Núñez, and Susana M. Mosca Copyright © 2013 Luisa F. González Arbeláez et al. All rights reserved. Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions Mon, 28 Oct 2013 18:12:43 +0000 In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2) expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs) culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2–24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis. Masami Fujisaki, Tomohisa Nagoshi, Tetsuo Nishikawa, Taro Date, and Michihiro Yoshimura Copyright © 2013 Masami Fujisaki et al. All rights reserved. Pulmonary Hypertension in Portugal: First Data from a Nationwide Registry Mon, 21 Oct 2013 08:11:07 +0000 Introduction. Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. Methods. We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). Results. Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 ± 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 ± 5.9 mmHg) and mean pulmonary vascular resistance (11.4 ± 6.5 Wood units), with a low cardiac index (2.7 ± 1.1 L·min−1·m−2); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 ± 12.5 years) and had higher RAP (11.0 ± 5.2 mmHg, ). Conclusions. We describe for the first time nationwide data on the diagnosis, management, and prognosis of PAH and CTEPH patients in Portugal. Clinical presentation and outcomes are comparable with those reported on other national registries. Rui Baptista, José Meireles, Ana Agapito, Graça Castro, António Marinho da Silva, Teresa Shiang, Fabienne Gonçalves, Susana Robalo-Martins, António Nunes-Diogo, and Abílio Reis Copyright © 2013 Rui Baptista et al. All rights reserved. Cardiometabolic Diseases and Related Complications: Current Status and Future Perspective Wed, 09 Oct 2013 11:21:46 +0000 Joseph Fomusi Ndisang and Sharad Rastogi Copyright © 2013 Joseph Fomusi Ndisang and Sharad Rastogi. All rights reserved. Association of the KLF14 rs4731702 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations Mon, 30 Sep 2013 08:14:31 +0000 The objective of the present study was to detect the association of the rs4731702 single nucleotide polymorphism (SNP) and serum lipid levels in the Guangxi Mulao and Han populations. A total of 727 subjects of Mulao and 740 subjects of Han Chinese were included. Serum low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels were higher in Mulao than in Han (). The T allele carriers had higher serum LDL-C and ApoAI levels in Mulao, whereas they had lower high-density lipoprotein cholesterol (HDL-C) levels and ratio of ApoAI to ApoB in Han () than the T allele noncarriers. Subgroup analyses showed that the T allele carriers had higher HDL-C, LDL-C, and ApoAI levels in Mulao males and lower ApoAI levels and ratio of ApoAI to ApoB in Han males than the T allele noncarriers. The subjects with TT genotype in Han females also had higher total cholesterol, LDL-C, ApoAI, and ApoB levels than the subjects with CT or CC genotype. Serum lipid parameters were also correlated with several environmental factors in both ethnic groups. The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions. Ping Huang, Rui-Xing Yin, Ke-Ke Huang, Xiao-Na Zeng, Tao Guo, Quan-Zhen Lin, Jian Wu, Dong-Feng Wu, Hui Li, and Shang-Ling Pan Copyright © 2013 Ping Huang et al. All rights reserved. First Evidence of Increased Plasma Serotonin Levels in Tako-Tsubo Cardiomyopathy Mon, 23 Sep 2013 08:57:12 +0000 Background. There is no data about the serotonergic activity during the acute phase of Tako-Tsubo Cardiomyopathy (TTC). The objective of our study was to investigate evidence of serotonin release from patients with TTC in comparison with patients with ST elevation myocardial infarction (STEMI) and healthy control subjects (HCS). Methods and Results. Plasma serotonin levels in 14 consecutive patients with TTC were compared with those in 14 patients with STEMI and 14 HCS. Plasma serotonin levels at admission were markedly higher in patients with TTC and STEMI as compared to HCS (, versus control; , versus control; and  ng/mL, resp.). There was no difference in serotonin levels between patients with TTC and those with STEMI (). Conclusion. This finding suggests that serotonin could participate to the pathophysiology of TTC. C. Rouzaud Laborde, C. Delmas, J. Mialet-Perez, N. Pizzinat, C. Biendel-Picquet, N. Boudou, N. Dumonteil, O. Spreux-Varoquaux, D. Carrié, M. Galinier, A. Parini, and O. Lairez Copyright © 2013 C. Rouzaud Laborde et al. All rights reserved. Feasibility, Reproducibility, and Agreement between Different Speckle Tracking Echocardiographic Techniques for the Assessment of Longitudinal Deformation Sun, 22 Sep 2013 11:28:22 +0000 Background. Left ventricular (LV) longitudinal deformation can be assessed with new echocardiographic techniques like triplane echocardiography (3PE) and four-dimensional echocardiography (4DE). We aimed to assess the feasibility, reproducibility, and agreement between these different speckle-tracking techniques for the assessment of longitudinal deformation. Methods. 101 consecutive subjects underwent echocardiographic examination. 2D cine loops from the apical views, a triplane view, and an LV 4D full volume were acquired in all subjects. LV longitudinal strain was obtained for each imaging modality. Results. 2DE analysis of LV strain was feasible in 90/101 subjects, 3PE strain in 89/101, and 4DE strain in 90/101. The mean value of 2DE and 3PE longitudinal strains was significantly higher with respect to 4DE. The relationship between 2DE and 3PE derived strains () was significantly higher (, ) than that between 2DE and 4DE () and that between 3PE and 4DE (; , ). The mean bias between 2DE and 4DE strains was while between 3PE and 4DE strains; the bias between 2DE and 3PE strain was of . Intraobserver and interobserver variabilities were acceptable among the techniques. Conclusions. Echocardiographic techniques for the assessment of longitudinal deformation are not interchangeable, and further studies are needed to assess specific reference values. Sergio Buccheri, Ines Monte, Sarah Mangiafico, Vera Bottari, Stefano Leggio, and Corrado Tamburino Copyright © 2013 Sergio Buccheri et al. All rights reserved. Does Off-Pump Coronary Artery Bypass Grafting Negatively Impact Long-Term Survival and Freedom from Reintervention? Wed, 11 Sep 2013 10:31:14 +0000 Recently published evidence has raised concerns about worse late mortality and increasing need for reintervention after off-pump coronary artery bypass grafting. We undertook this study to assess the impact of off-pump coronary artery bypass grafting on survival and freedom from reintervention at 10 years. From January 2002 to December 2002, 307 consecutive patients who had isolated multivessel off-pump coronary artery bypass grafting at our institution were compared to a control group of 397 patients that underwent multivessel on-pump coronary artery bypass grafting during the same period. In addition, univariate and risk-adjusted comparisons between the two groups were performed at 10 years. Kaplan-Meier survival was similar for the two cohorts. After adjusting for clinical covariates, off-pump coronary artery bypass grafting did not emerge as a significant independent predictor of long-term mortality (Hazard Ratio 0.91; 95% Confidence Interval 0.70–1.12), readmission to hospital for cardiac cause (Hazard Ratio 0.96; 95% Confidence Interval 0.78–1.10), or the need for reintervention (Hazard Ratio 0.93; 95% Confidence Interval 0.87–1.05). Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting does not adversely impact survival or freedom from reintervention at a 10-year follow-up. Shahzad G. Raja, Mubassher Husain, Florentina L. Popescu, Dimple Chudasama, Siobhan Daley, and Mohamed Amrani Copyright © 2013 Shahzad G. Raja et al. All rights reserved. Periodontal Disease Is an Independent Predictor of Intracardiac Calcification Wed, 11 Sep 2013 10:11:07 +0000 Background. Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. Hypothesis. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Methods. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Results. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, ) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (). There was no significant interaction by study site, race, or gender. Conclusions. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification. Gregg S. Pressman, Atif Qasim, Nitin Verma, Masami Miyamae, Kumiko Arishiro, Yasuhiro Notohara, Vitalie Crudu, and Vincent M. Figueredo Copyright © 2013 Gregg S. Pressman et al. All rights reserved. Determinants of Thyrotoxic Cardiomyopathy Recovery Sun, 08 Sep 2013 15:13:45 +0000 The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment. Lucia Oliveros-Ruiz, Maite Vallejo, L. Fernando Diez Canseco, Manuel Cárdenas, and J. Antonio G. Hermosillo Copyright © 2013 Lucia Oliveros-Ruiz et al. All rights reserved. Materials and Manufacturing Technologies Available for Production of a Pediatric Bioabsorbable Stent Sun, 08 Sep 2013 14:49:37 +0000 Transcatheter treatment of children with congenital heart disease such as coarctation of the aorta and pulmonary artery stenosis currently involves the use of metal stents. While these provide good short term results, there are long term complications with their use. Children outgrow metal stents, obligating them to future transcatheter dilations and eventual surgical removal. A bioabsorbable stent, or a stent that goes away with time, would solve this problem. Bioabsorbable stents are being developed for use in coronary arteries, however these are too small for use in pediatric congenital heart disease. A bioabsorbable stent for use in pediatric congenital heart disease needs to be low profile, expandable to a diameter 8 mm, provide sufficient radial strength, and absorb quickly enough to allow vessel growth. Development of absorbable coronary stents has led to a great understanding of the available production techniques and materials such as bioabsorbable polymers and biocorrodable metals. Children with congenital heart disease will hopefully soon benefit from the current generation of bioabsorbable and biocorrodable materials and devices. Ryan D. Alexy and Daniel S. Levi Copyright © 2013 Ryan D. Alexy and Daniel S. Levi. All rights reserved. Influence of Positive End-Expiratory Pressure on Myocardial Strain Assessed by Speckle Tracking Echocardiography in Mechanically Ventilated Patients Wed, 28 Aug 2013 16:06:23 +0000 Purpose. The effects of mechanical ventilation (MV) on speckle tracking echocardiography- (STE-)derived variables are not elucidated. The aim of the study was to evaluate the effects of positive end-expiratory pressure (PEEP) ventilation on 4-chamber longitudinal strain (LS) analysis by STE. Methods. We studied 20 patients admitted to a mixed intensive care unit who required intubation for MV and PEEP titration due to hypoxia. STE was performed at three times: (T1) PEEP = 5 cmH2O; (T2) PEEP = 10 cmH2O; and (T3) PEEP = 15 cmH2O. STE analysis was performed offline using a dedicated software (XStrain MyLab 70 Xvision, Esaote). Results. Left peak atrial-longitudinal strain (LS) was significantly reduced from T1 to T2 and from T2 to T3 (). Right peak atrial-LS and right ventricular-LS showed a significant reduction only at T3 (). Left ventricular-LS did not change significantly during titration of PEEP. Cardiac chambers’ volumes showed a significant reduction at higher levels of PEEP (). Conclusions. We demonstrated for the first time that incremental PEEP affects myocardial strain values obtained with STE in intubated critically ill patients. Whenever performing STE in mechanically ventilated patients, care must be taken when PEEP is higher than 10 cmH2O to avoid misinterpreting data and making erroneous decisions. Federico Franchi, Agnese Faltoni, Matteo Cameli, Luigi Muzzi, Matteo Lisi, Lucia Cubattoli, Sofia Cecchini, Sergio Mondillo, Bonizella Biagioli, Fabio Silvio Taccone, and Sabino Scolletta Copyright © 2013 Federico Franchi et al. All rights reserved. A New Coated Nitinol Occluder for Transcatheter Closure of Ventricular Septal Defects in a Canine Model Tue, 27 Aug 2013 13:52:25 +0000 Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs () as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, , Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization. Yong Zhou, Feng Chen, Xinmiao Huang, Xianxian Zhao, Hong Wu, Yuan Bai, and Yongwen Qin Copyright © 2013 Yong Zhou et al. All rights reserved. End-Systolic Elastance and Ventricular-Arterial Coupling Reserve Predict Cardiac Events in Patients with Negative Stress Echocardiography Mon, 19 Aug 2013 09:09:28 +0000 Background. A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography. Methods. We enrolled 891 patients (593 males mean age , ejection fraction ), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (), ventricular arterial coupling (VAC) indexed by the ratio of the to arterial elastance index (), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization. Results. During a median followup of 19 months (interquartile range 8–36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole. Conclusions. Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of reserve and VAC reserve during stress echo. Tonino Bombardini, Marco Fabio Costantino, Rosa Sicari, Quirino Ciampi, Lorenza Pratali, and Eugenio Picano Copyright © 2013 Tonino Bombardini et al. All rights reserved. Sleep-Disordered Breathing in Patients with Heart Failure: New Trends in Therapy Sun, 28 Jul 2013 15:46:45 +0000 Heart failure (HF) is a growing health problem which paradoxically results from the advances in the treatment of etiologically related diseases (especially coronary artery disease). HF is commonly accompanied by sleep-disordered breathing (SDB), which may directly exacerbate the clinical manifestations of cardiovascular disease and confers a poorer prognosis. Obstructive sleep apnoea predominates in mild forms while central sleep apnoea in more severe forms of heart failure. Identification of SDB in patients with HF is important, as its effective treatment may result in notable clinical benefits to the patients. Continuous positive airway pressure (CPAP) is the gold standard in the management of SDB. The treatments for central breathing disorders include CPAP, bilevel positive airway pressure (BPAP), and adaptive servoventilation (ASV), with the latter being the most modern method of treatment for the Cheyne-Stokes respiration and involving ventilation support with a variable synchronisation dependent on changes in airflow through the respiratory tract and on the patient’s respiratory rate. ASV exerts the most favourable effect on long-term prognosis. In this paper, we review the current state of knowledge on the diagnosis and treatment of SDB with a particular emphasis on the latest methods of treatment. Anna Kazimierczak, Paweł Krzesiński, Krystian Krzyżanowski, and Grzegorz Gielerak Copyright © 2013 Anna Kazimierczak et al. All rights reserved. Pharmacodynamic Effect of Clopidogrel in Patients Undergoing Transcatheter Aortic Valve Implantation Mon, 15 Jul 2013 11:23:59 +0000 The aim of this study was to analyze periprocedural and mid-term effect of clopidogrel on platelet function using the VerifyNow P2Y12 point-of-care assay in patients undergoing TAVI. Platelet reactivity was measured at the beginning of the procedure after 300 mg clopidogrel bolus administration and during the follow-up (at 1 month after the procedure) in 52 patients undergoing TAVI using the Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU was used to identify nonresponders to clopidogrel treatment with high residual platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and in 72% of patients during 6-month follow-up. There was no significant difference in the pharmacodynamic effects of clopidogrel on platelet reactivity from baseline to 6-months follow-up ( vs. ; ). Ischemic event occurred only in 3 patients (5.8%) from the study group. In conclusion, majority of patients undergoing TAVI had high residual platelet reactivity after pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI population raises the question of the routine use of dual antiplatelet treatment in this setting. Petr Tousek, Viktor Kocka, Jakub Sulzenko, Frantisek Bednar, Hana Linkova, and Petr Widimsky Copyright © 2013 Petr Tousek et al. All rights reserved. Transcriptomic Profiling of the Four Adenosine Receptors in Human Leukocytes of Heart Failure Patients Mon, 08 Jul 2013 13:40:06 +0000 In this study the transcriptomic profiling of adenosine receptors (ARs) in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (), was evaluated. Total RNA was extracted from leukocytes of () and of HF patients (NYHA I-II ; NYHA III-IV ) with a PAXgene Blood RNA Kit. An increase as a function of clinical severity was observed in each AR (A1R: , NYHA , NYHA ,    versus NYHA III-IV, NYHA I-II versus NYHA III-IV; A2aR: , NYHA , NYHA ,    versus NYHA III-IV, NYHA I-II versus NYHA III-IV; A2bR: , NYHA , NYHA , : NYHA I-II versus NYHA III-IV; A3R: , NYHA , NYHA ,    versus NYHA III-IV and NYHA I-II versus NYHA III-IV, resp.). The mRNA expression of the ectonucleoside triphosphate diphosphohydrolase (CD39) and the ecto-5′-nucleotidase (CD73) were also evaluated. They resulted up-regulated. These findings show that components of adenosine metabolism and signalling are altered to promote adenosine production and signalling in HF patients. Thus, HF may benefit from adenosine-based drug therapy after confirmation by clinical trials. Manuela Cabiati, Raffaele Caruso, Alessandro Verde, Laura Sabatino, Maria-Aurora Morales, and Silvia Del Ry Copyright © 2013 Manuela Cabiati et al. All rights reserved. Mechanostimulation Protocols for Cardiac Tissue Engineering Mon, 08 Jul 2013 09:51:57 +0000 Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field. Marco Govoni, Claudio Muscari, Carlo Guarnieri, and Emanuele Giordano Copyright © 2013 Marco Govoni et al. All rights reserved. Detection of Gender Differences in Incomplete Revascularization after Coronary Artery Bypass Surgery Varies with Classification Technique Mon, 08 Jul 2013 08:47:55 +0000 Background. Incomplete revascularization negatively affects survival after coronary artery bypass surgery (CABG). Since gender and classification technique might impact outcome and reporting, we investigated their effect on revascularization patterns and mortality. Methods. A cohort of bypass patients (, 23% women) was enrolled prospectively. The degree of revascularization was determined as mathematical difference between affected vessels upon diagnosis and number of grafts or the surgeon’s rating on the case file. Results. Although men displayed more triple-vessel disease, they obtained complete revascularization more frequently than women (85% versus 77%, ). The two calculation methods identified analogous percentages of incompletely revascularized patients, yet there was only a 50% overlap between the two groups. Mathematically, more women, older patients, and patients with NYHA class III/IV appeared incompletely revascularized, while the surgeons identified more patients undergoing technically challenging procedures. Regardless of the definition, incompleteness was a significant risk factor for mortality in both genders (mathematical calculation: HR 2.62, 95% CI 1.76–3.89, ; surgeon: HR 2.04, 95% CI 1.35–3.89, ). Conclusions. Given the differences in identification patterns, we advise that the mathematical calculation be performed after-procedure in all patients regardless of the surgeons’ rating to uncover additional subjects at increased risk. Sabine Oertelt-Prigione, Friederike Kendel, Martin Kaltenbach, Roland Hetzer, Vera Regitz-Zagrosek, and Rufus Baretti Copyright © 2013 Sabine Oertelt-Prigione et al. All rights reserved. Quantitative PCR as an Alternative in the Diagnosis of Long-QT Syndrome Tue, 02 Jul 2013 11:17:11 +0000 Congenital long-QT syndrome is a genetic disorder associated with abnormalities in the function and/or structure of cardiac ion channels. Up to the present, 13 types of the disease have been described (LQTS1-13) which result from the fact that 13 genes of which mutations can have an influence on the occurrence of the disease have been identified. Characteristic symptoms of the disease include the changes in the ECG (QT interval prolonged above 450 ms), “torsade de pointes,” fainting, and even sudden cardiac death. The present study has been focused on two types of the disease, namely, LQTS1 and LQTS2. The examination of two appropriate genes expression (KCNQ1; KCNH2) at the transcription level by QRT-PCR in a group of LQTS patients and a healthy control group showed different transcriptional activities of KCNH2 gene in LQTS2 patients compared to the control individuals. KCNQ1 gene expression study did not reveal such differences between both groups. The results indicate that QRT-PCR may serve as a complimentary method to the identification of molecular alterations in genetic determinants of LQTS2 only, but it cannot be used as a sole diagnostic criterion. Ewa Moric-Janiszewska, Ludmiła Węglarz, and Magdalena Szczurko Copyright © 2013 Ewa Moric-Janiszewska et al. All rights reserved. Echocardiography in the Era of Multimodality Cardiovascular Imaging Wed, 26 Jun 2013 11:34:05 +0000 Echocardiography remains the most frequently performed cardiac imaging investigation and is an invaluable tool for detailed and accurate evaluation of cardiac structure and function. Echocardiography, nuclear cardiology, cardiac magnetic resonance imaging, and cardiovascular-computed tomography comprise the subspeciality of cardiovascular imaging, and these techniques are often used together for a multimodality, comprehensive assessment of a number of cardiac diseases. This paper provides the general cardiologist and physician with an overview of state-of-the-art modern echocardiography, summarising established indications as well as highlighting advances in stress echocardiography, three-dimensional echocardiography, deformation imaging, and contrast echocardiography. Strengths and limitations of echocardiography are discussed as well as the growing role of real-time three-dimensional echocardiography in the guidance of structural heart interventions in the cardiac catheter laboratory. Benoy Nalin Shah Copyright © 2013 Benoy Nalin Shah. All rights reserved. Therapeutic Application of Cardiac Stem Cells and Other Cell Types Wed, 26 Jun 2013 11:29:45 +0000 Various researches on regenerative medicine were carried out experimentally, and selected modalities have been introduced to the clinical arena. Meanwhile, the presence of resident stem cells in the heart and their role in physiological cell turnover were demonstrated. So far skeletal myoblasts, bone marrow-derived cells, mesenchymal stromal cells, and resident cardiac cells have been applied for therapeutic myocardial regeneration. Among them, autologous transplantation of c-kit-positive cardiac stem cells in congestive heart failure patients resulted in an outstanding outcome, with long-lasting beneficial effects without major adverse events. By reviewing these clinical trials, an endeavor was made to seek for an ideal cellular therapy for cardiovascular diseases. Emiko Hayashi and Toru Hosoda Copyright © 2013 Emiko Hayashi and Toru Hosoda. All rights reserved. Effects of Community-Based Cardiac Rehabilitation on Body Composition and Physical Function in Individuals with Stable Coronary Artery Disease: 1.6-Year Followup Tue, 25 Jun 2013 17:05:21 +0000 Objective. To examine long-term changes in physical function and body composition in coronary artery disease (CAD) patients participating in ongoing community-based cardiac rehabilitation (CR). Design. Thirty-four individuals ( years; 79% men) participated in this longitudinal observational study. Baseline and follow-up assessments included incremental shuttle walk, short physical performance battery, handgrip strength, chair stands, body composition, last year physical activity, and CR attendance. Results. Participants attended sessions during year followup. A significant increase in 30-second chair stands ( to , ), body weight ( to  kg, ), and body fat ( to %, ) and a decline in handgrip strength ( to kg·f, ) and muscle mass ( to %, ) were observed during followup. There was no significant change in shuttle walk duration. CR attendance was not correlated to observed changes. Conclusions. Elderly CAD patients participating in a maintenance CR program improve lower-body muscle strength but experience a decline in handgrip strength and unfavourable changes in body composition, irrespective of CR attendance. Sandra Mandic, Claire Hodge, Emily Stevens, Robert Walker, Edwin R. Nye, Dianne Body, Leanne Barclay, and Michael J. A. Williams Copyright © 2013 Sandra Mandic et al. All rights reserved. Cardiovascular Profile of Xanthelasma Palpebrarum Thu, 20 Jun 2013 18:03:12 +0000 Xanthelasma palpebrarum (XP) are yellow plaques that occur most commonly near the inner canthus of the eyelid and are often associated with atherosclerosis, dyslipidemia, and coronary artery disease. This study was planned to address the issue of associated cardiovascular morbidity in xanthelasma patients attending our cardiac clinic. Materials and Methods. A total of 61 patients were detected to be having xanthelasma and constituted the study group. The control group constituted of 130 apparently normal individuals. Each patient underwent detailed history, examination, and investigations. Results and Discussion. The most prevalent age group was 40 to 60 years. Males outnumbered females. A percentage of 39.3% of cases had concomitant nicotine addiction. Dyslipidemia was present in 60% of cases, hypertension in 37.7%, prehypertension in 8.77%, diabetes mellitus in 18.03%, and prediabetes in 26.3%. Smokers and obese patients with xanthelasma had a higher prevalence of hypertension. Coronary artery disease (CAD) was found in 6.56% of XP cases. The waist circumference and diastolic blood pressures were significantly higher in XP patients. Conclusion. A significant number of cases of xanthelasma palpebrarum are combined with smoking, central obesity, hypertension, diabetes mellitus, and dyslipidemia which are the major risk factors for CAD. Efforts should be made to rule out the same in high-risk xanthelasma subjects. Anupam Dey, Ramesh Aggarwal, and Shridhar Dwivedi Copyright © 2013 Anupam Dey et al. All rights reserved. Carotid Artery Segmentation in Ultrasound Images and Measurement of Intima-Media Thickness Thu, 20 Jun 2013 08:54:18 +0000 Background. The segmentation of the common carotid artery (CCA) wall is imperative for the determination of the intima-media thickness (IMT) on B-mode ultrasound (US) images. The IMT is considered an important indicator in the evaluation of the risk for the development of atherosclerosis. In this paper, authors have discussed the relevance of measurements in clinical practices and the challenges that one has to face while approaching the segmentation of carotid artery on ultrasound images. The paper presents an overall review of commonly used methods for the CCA segmentation and IMT measurement along with the different performance metrics that have been proposed and used for performance validation. Summary and future directions are given in the conclusion. Vaishali Naik, R. S. Gamad, and P. P. Bansod Copyright © 2013 Vaishali Naik et al. All rights reserved. Ventricular Dyssynchrony and Function Improve following Catheter Ablation of Nonseptal Accessory Pathways in Children Tue, 18 Jun 2013 16:15:45 +0000 Introduction. Paradoxical or hypokinetic interventricular septal motion has been described in patients with septal or paraseptal accessory pathways. Data regarding nonseptal pathways is limited. Methods and Results. We quantified left ventricular dyssynchrony and function in 16 consecutive children, years, weighing  kg, prior to and following catheter ablation of bidirectional septal () and nonseptal () accessory pathways. Following ablation, the left ventricular ejection fraction increased by % () from a baseline value of . By tissue Doppler imaging, the interval between QRS onset and peak systolic velocity (Ts) decreased from a median of 33.0 ms to 18.0 ms (). The left ventricular ejection fraction increased to a greater extent following catheter ablation of nonseptal (, ) versus septal (, ) pathways. The four patients with an ejection fraction <50%, two of whom had left lateral pathways, improved to >50% after ablation. Similarly, the improvement in dyssynchrony was more marked in patients with nonseptal versus septal pathways (difference between septal and lateral wall motion delay before and after ablation  ms () versus  ms ()). Conclusion. Left ventricular systolic function and dyssynchrony improve after ablation of antegrade-conducting accessory pathways in children, with more pronounced changes noted for nonseptal pathways. Sylvia Abadir, Anne Fournier, Marc Dubuc, Georgia Sarquella-Brugada, Patrick Garceau, and Paul Khairy Copyright © 2013 Sylvia Abadir et al. All rights reserved. Pregnancy after Acute Coronary Syndrome: A Proposal for Patients’ Management and a Literature Review Thu, 06 Jun 2013 17:43:47 +0000 Coronary artery disease complicates only 0.01% of all pregnancies. For this reason, more exhaustive data on the management of such cases is lacking. Even guidelines on management of cardiovascular disease in pregnant women are scarce focusing mainly on acute myocardial infarction. This is a complex issue involving thorough evaluation of cardiovascular status in each pregnant woman, assessment of risk for developing coronary complications, and close cooperation with obstetric teams. Safety data on typical cardiac drugs such as statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or novel antiplatelet drugs are also scarce and their effect on the developing human fetus is not well understood. We present a review on the management of such patients. Agnieszka Janion-Sadowska, Marcin Sadowski, Jacek Kurzawski, Łukasz Zandecki, and Marianna Janion Copyright © 2013 Agnieszka Janion-Sadowska et al. All rights reserved. High-Dose, but Not Low-Dose, Aspirin Impairs Anticontractile Effect of Ticagrelor following ADP Stimulation in Rat Tail Artery Smooth Muscle Cells Thu, 06 Jun 2013 17:42:14 +0000 Objective. To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular smooth muscle cells (VSMCs). Methods. Wistar rats were orally administered ticagrelor (10 mg/kg) and/or aspirin (2 or 10 mg/kg) ( per each of 4 groups) or placebo () 12 and 2 hours before experiments. Anticontractile effects of ticagrelor were assessed in perfusion solution containing ticagrelor (1 μM/L). Changes in perfusion pressure proportional to the degree of adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated. Results. Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels. Suppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was maintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose aspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response curve for phenylephrine. With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect. Conclusion. High-dose, but not low-dose, aspirin impairs the anticontractile effect of ticagrelor on ADP-induced VSMC contraction in the rat model. Both the clinical significance and detailed underlying mechanism of our findings require further investigation. Grzegorz Grześk, Marek Kozinski, Udaya S. Tantry, Michal Wicinski, Tomasz Fabiszak, Eliano P. Navarese, Elzbieta Grzesk, Young-Hoon Jeong, Paul A. Gurbel, and Jacek Kubica Copyright © 2013 Grzegorz Grześk et al. All rights reserved. Expression and Complex Formation of MMP9, MMP2, NGAL, and TIMP1 in Porcine Myocardium but Not in Skeletal Muscles in Male Pigs with Tachycardia-Induced Systolic Heart Failure Mon, 22 Apr 2013 10:43:38 +0000 Matrix metalloproteinases (MMPs) are involved in the remodeling of extracellular matrix in various tissues. Their functioning could be related to the formation of complexes, containing MMP9, MMP2, tissue inhibitor of metalloproteinases type 1 (TIMP1), and neutrophil gelatinase-associated lipocalin (NGAL). Such complexes have not been investigated in either myocardial or skeletal muscles. We examined 20 male pigs with heart failure (HF), and 5 sham-operated animals. There were no differences in the mRNA expression of MMP9, MMP2, TIMP1, and NGAL between diseased and healthy animals, in either left ventricle (LV) myocardium or skeletal muscles. In LV from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we demonstrated the presence of high molecular weight (HMW) complexes (130, 170, and 220 kDa) containing MMP9, TIMP1, and NGAL (also MMP2 in 220 kDa complex) without proteolytic activity, and a proteolytically active 115 kDa MMP9 form together with 72 and 68 kDa bands (proMMP2 and MMP2). Proteolytically active bands were also spontaneously released from HMW complexes. In skeletal muscles from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we found no HMW complexes, and proteolytic activity was associated with the presence of 72 and 68 kDa bands (proMMP2 and MMP2). Liliana Kiczak, Alicja Tomaszek, Jacek Bania, Urszula Paslawska, Maciej Zacharski, Agnieszka Noszczyk-Nowak, Adrian Janiszewski, Piotr Skrzypczak, Hossein Ardehali, Ewa A. Jankowska, and Piotr Ponikowski Copyright © 2013 Liliana Kiczak et al. All rights reserved. A Novel Technique for the Assessment of Preoperative Cardiovascular Risk: Reactive Hyperemic Response to Short-Term Exercise Wed, 10 Apr 2013 14:21:08 +0000 Background. Perioperative vascular function has been widely studied using noninvasive techniques that measure reactive hyperemia as a surrogate marker of vascular function. However, studies are limited to a static setting with patients tested at rest. We hypothesized that exercise would increase reactive hyperemia as measured by digital thermal monitoring (DTM) in association to patients' cardiometabolic risk. Methods. Thirty patients (58 ± 9 years) scheduled for noncardiac surgery were studied prospectively. Preoperatively, temperature rebound (TR) following upper arm cuff occlusion was measured before and 10 minutes after exercise. Data are presented as means ± SD. Statistical analysis utilized ANOVA and Fisher’s exact test, with values <0.05 regarded as significant. Results. Following exercise, TR-derived parameters increased significantly (absolute: 0.53 ± 0.95 versus 0.04 ± 0.42∘C, , and % change: 1.78 ± 3.29 versus 0.14 ± 1.27 %, ). All patients with preoperative cardiac risk factors had a change in TR (after/before exercise, ΔTR) with values falling in the lower two tertiles of the study population (TR %). Conclusion. Exercise increased the reactive hyperemic response to ischemia. This dynamic response was blunted in patients with cardiac risk factors. The usability of this short-term effect for the preoperative assessment of endothelial function warrants further study. Robert Schier, Jochen Hinkelbein, Hanke Marcus, Ashley Smallwood, Arlene M. Correa, Reza Mehran, Randa El-Zein, and Bernhard Riedel Copyright © 2013 Robert Schier et al. All rights reserved. A Systematic Review of Effects of Concurrent Strength and Endurance Training on the Health-Related Quality of Life and Cardiopulmonary Status in Patients with HIV/AIDS Wed, 03 Apr 2013 11:22:50 +0000 Purpose. To determine the effects of concurrent strength and endurance training (concurrent training) on the Health-Related Quality of Life (HRQOL) and cardiopulmonary status among HIV-infected patients, using a systematic search strategy of randomized, controlled trials (RCTs). Methods. A systematic review was performed by two independent reviewers using Cochrane Collaboration protocol. The sources used in this review were Cochrane Library, EMBASE, LILACS, MEDLINE, PEDro and Web of Science from 1950 to August 2012. The PEDro score was used to evaluate methodological quality. Result. Individual studies suggested that concurrent training contributed to improved HRQOL and cardiovascular status. Concurrent training appears to be safe and may be beneficial for medically stable adults living with HIV. The rates of nonadherence were of 16%. Conclusion. Concurrent training improves the HRQOL and cardiopulmonary status. It may be an important intervention in the care and treatment of adults living with HIV. Further research is needed to determine the minimal and optimal duration, frequency, and intensity of exercise needed to produce beneficial changes in the HIV-infected population subgroups. Mansueto Gomes Neto, Cecília Ogalha, Antônio Marcos Andrade, and Carlos Brites Copyright © 2013 Mansueto Gomes Neto et al. All rights reserved. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome Mon, 18 Mar 2013 09:47:59 +0000 Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome. Christine G. Schnackenberg, Melissa H. Costell, Daniel J. Krosky, Jianqi Cui, Charlene W. Wu, Victor S. Hong, Mark R. Harpel, Robert N. Willette, and Tian-Li Yue Copyright © 2013 Christine G. Schnackenberg et al. All rights reserved. Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein Graft In Vivo Sun, 17 Mar 2013 14:31:43 +0000 The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz) as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft. Chengwei Liu, Xuesong Zhang, Shi Wang, Mingxun Cheng, Chuanyu Liu, Shuqing Wang, Xinhua Hu, and Qiang Zhang Copyright © 2013 Chengwei Liu et al. All rights reserved. A Case-Control Study between Gene Polymorphisms of Polyunsaturated Fatty Acid Metabolic Rate-Limiting Enzymes and Acute Coronary Syndrome in Chinese Han Population Thu, 28 Feb 2013 10:53:45 +0000 The purpose of this study is to analyze the relationship between the polymorphisms of fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very long-chain fatty acids-like 2 (ELOVL2) and acute coronary syndrome (ACS) in Chinese Han population. Therefore, we selected three single nucleotide polymorphisms (SNPs) from these candidate genes and genotyped them using PCR-based restriction fragment length polymorphism analysis in 249 ACS patients and 240 non-ACS subjects, as were Han Chinese ancestry. The results showed that rs174556 in the FADS1 gene is found to be in allelic association () and genotypic association () with ACS. The frequencies of rs174556 minor allele (T) in case group were obviously higher than in control group. The trans-phase gene-gene interaction analysis showed that the combined genotype of rs174556 (T/T) and rs3756963 (T/T) was associated with ACS (). And the results suggest that, for rs174556 C>T, the CT/TT genotypes were more likely to lead in ACS in subjects with hypertension after correction of all risk factors (, 95% CI, 2.216–7.126). These findings suggest that the polymorphisms of rs174556 in the FADS1 gene are very likely to be associated with ACS in Chinese Han population, especially in subjects with hypertension. Zikai Song, Hongyan Cao, Ling Qin, and Yanfang Jiang Copyright © 2013 Zikai Song et al. All rights reserved. The Use of Continuous Glucose Monitoring Combined with Computer-Based eMPC Algorithm for Tight Glucose Control in Cardiosurgical ICU Wed, 20 Feb 2013 15:08:00 +0000 Aim. In postcardiac surgery patients, we assessed the performance of a system for intensive intravenous insulin therapy using continuous glucose monitoring (CGM) and enhanced model predictive control (eMPC) algorithm. Methods. Glucose control in eMPC-CGM group () was compared with a control (C) group () treated by intravenous insulin infusion adjusted according to eMPC protocol with a variable sampling interval alone. In the eMPC-CGM group glucose measured with a REAL-Time CGM system (Guardian RT) served as input for the eMPC adjusting insulin infusion every 15 minutes. The accuracy of CGM was evaluated hourly using reference arterial glucose and Clarke error-grid analysis (C-EGA). Target glucose range was 4.4–6.1 mmol/L. Results. Of the 277 paired CGM-reference glycemic values, 270 (97.5%) were in clinically acceptable zones of C-EGA and only 7 (2.5%) were in unacceptable D zone. Glucose control in eMPC-CGM group was comparable to C group in all measured values (average glycemia, percentage of time above, within, and below target range,). No episode of hypoglycemia (<2.9 mmol) occurred in eMPC-CGM group compared to 2 in C group. Conclusion. Our data show that the combination of eMPC algorithm with CGM is reliable and accurate enough to test this approach in a larger study population. Petr Kopecký, Miloš Mráz, Jan Bláha, Jaroslav Lindner, Štĕpán Svačina, Roman Hovorka, and Martin Haluzík Copyright © 2013 Petr Kopecký et al. All rights reserved. Human Resistin Inhibits Myogenic Differentiation and Induces Insulin Resistance in Myocytes Mon, 18 Feb 2013 08:58:32 +0000 This study is aimed to investigate the effect of human resistin on myocyte differentiation and insulin resistance. The human resistin eukaryotic expression vector was stable transfected into C2C12 myocyte cells and was transiently transfected into COS7 cells. The effects of human resistin on cell proliferation, cell cycle, and myogenic differentiation of C2C12 cells were examined. Glucose uptake assays was performed on C2C12 myotubes by using [3H] 2-deoxy-D-glucose. The mRNA levels of insulin receptor (IR) and glucose transporter 4 (GLUT4) were evaluated by semiquantitative RT-PCR. Results showed by the C2C12 cells transfected with human resistin gene compared with that without transfecting gene are as follows: (1) cell proliferation was significantly promoted, (2) after inducing differentiation, the myotube’s diameters and expression of desmin and myoglobin decreased, and (3) glucose uptake ratio was lowered and expression of IR and GLUT4 decreased. However, there was no significant difference in the glucose uptake ratio between C2C12 myotubes treated with a human resistin conditioned medium of COS7 cells and treated with control medium. These results suggest that maybe human resistin has not a direct role on insulin sensitivity of myocytes. However, maybe it impaired the insulin sensitivity of myocytes through suppressing myogenesis and stimulating proliferation of myoblasts. Chun Hua Sheng, Zhen Wu Du, Yang Song, Xiao Dong Wu, Yu Cheng Zhang, Mei Wu, Qian Wang, and Gui Zhen Zhang Copyright © 2013 Chun Hua Sheng et al. All rights reserved. A New Dual-Promoter System for Cardiomyocyte-Specific Conditional Induction of Apoptosis Thu, 31 Jan 2013 08:12:07 +0000 Apoptosis is a key determinant of major pathological processes, including chronic cardiac failure. We developed and tested in vitro a novel system to induce cardiomyocyte-specific apoptosis by virus-mediated delivery of a conditional transgene. The entire system was packaged in a lentiviral vector. We used the cardiomyocyte-specific Na+-Ca2+ exchange promoter to control the transcription of the reverse tetracycline transactivator, while the transgene expression was driven by the tetracycline-responsive element. The proapoptotic transgene of choice was the short isoform of the apoptosis-inducing factor, known to quickly induce the caspase-independent apoptosis when overexpressed in cells. Transduction of cardiomyocyte cells with this vector caused a tetracycline-regulated induction of apoptosis, which was not observed in noncardiac cells. Therefore, our system proved a valuable molecular tool for inducing controlled apoptosis in selected cells. Furthermore, the vector we developed is suitable for “lentivirus transgenesis,” an interesting strategy recently proposed for the genetic manipulation of animals other than mice, including large mammals. Silvia Agostini, Vincenzo Lionetti, Marco Matteucci, Flavia Chiuppesi, Mauro Giacca, Mauro Pistello, and Fabio A. Recchia Copyright © 2013 Silvia Agostini et al. All rights reserved. Anti-Inflammatory Effects of Arsenic Trioxide Eluting Stents in a Porcine Coronary Model Wed, 16 Jan 2013 19:15:27 +0000 Previous research from our group has demonstrated arsenic trioxide eluting stents significantly reduced neointimal area and thickness compared with bare metal stents. In the present study, the anti-inflammatory effects of arsenic trioxide in vitro and arsenic trioxide eluting stents in a porcine coronary model have been explored. Sixty-five pigs underwent placement of 139 oversized stents in the coronary arteries with histologic analysis, endothelial function analysis, and immunohistochemical and western blot analyses. Arsenic trioxide eluting stents effectively inhibited local inflammatory reactions, while no significant difference in endothelialization and endothelial function between arsenic trioxide eluting stents and bare metal stents was observed. Arsenic trioxide eluting stents favorably modulate neointimal formation due to less augmentation of early inflammatory reactions, and quick endothelialization of the stent surface, which might contribute to long-term safety and efficacy of drug eluting stents. Li Shen, Feirong Gong, Wenjie Tian, Weiming Li, Feng Zhang, Juying Qian, Aijun Sun, Yunzeng Zou, Wei Yang, and Junbo Ge Copyright © 2013 Li Shen et al. All rights reserved. Mulberry Leaf Reduces Oxidation and C-Reactive Protein Level in Patients with Mild Dyslipidemia Tue, 15 Jan 2013 11:42:54 +0000 C-reactive protein (CRP) is the inflammatory marker that could represent the inflammation in blood vessels resulted from dyslipidemia. The objective of this study was to evaluate the antioxidative activity of mulberry leaf powder using DPPH assay and the effect of mulberry leaf powder on lipid profile, CRP level, and antioxidative parameters in mild dyslipidemia patients. A within-subjects design was conducted and patients received three tablets of 280 mg mulberry leaf powder three times a day before meals for 12 weeks. Total of 25 patients were enrolled but one subject was excluded. After three months of mulberry leaf consumption, serum triglyceride and low-density lipoprotein (LDL) level were significantly reduced and more than half of all patients’ CRP levels decreased every month as well as the mean CRP level but no statistically significant difference was found. The average erythrocyte glutathione peroxidase activity of patients was increased but not at significant level; however, the mean serum 8-isoprostane level was significantly lower after mulberry treatment for 12 weeks. It can be concluded that mulberry leaf powder exhibited antioxidant activity and mulberry leaf powder has potential to decrease serum triglyceride, LDL, and CRP levels in mild dyslipidemia patients without causing severe adverse reactions. Pornanong Aramwit, Ouppatham Supasyndh, Tippawan Siritienthong, and Nipaporn Bang Copyright © 2013 Pornanong Aramwit et al. All rights reserved. Possible Role of Hyperinsulinemia and Insulin Resistance in Lower Vitamin D Levels in Overweight and Obese Patients Mon, 14 Jan 2013 15:39:09 +0000 A cohort of 66 healthy overweight and obese patients, 53 women and 13 men were examined. Waist circumference and fasting 25(OH)D, insulin, glucose, lipid (cholesterol, HDL cholesterol, and triglyceride), C-reactive protein (CRP), and complement 3 (C3), and 4 (C4) serum concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMAIR). Results. 25(OH)D levels showed a significant negative correlation with BMI (), waist circumference (), fasting insulin (), HOMAIR (), triglycerides (), CRP (), C3 (), and C4 (). Multiple regression analyses were performed with 25(OH)D as the dependent variable and BMI (or waist circumferences), fasting insulin (or HOMAIR), triglycerides, and CRP (or C3 or C4) as independent variables. Only insulin or HOMAIR maintained a significant independent association with 25(OH)D levels, whereas vitamin D did not maintain a significant independent association with CRP or C3 or C4 concentrations. Conclusions. The present study, performed in overweight and obese subjects, shows that 25(OH)D levels are negatively associated with inflammatory parameters such as CRP and C3 and C4 levels, but not independently of BMI, body fat distribution, insulin levels, or insulin resistance. Our results suggest that hyperinsulinemia and/or insulin resistance are directly responsible for decrease of 25(OH)D levels in obesity. Giovanni De Pergola, Alessandro Nitti, Nicola Bartolomeo, Antonella Gesuita, Vito Angelo Giagulli, Vincenzo Triggiani, Edoardo Guastamacchia, and Franco Silvestris Copyright © 2013 Giovanni De Pergola et al. All rights reserved. Serum Fetuin-A Levels Related with Microalbuminuria in Diet-Induced Obese Rats Mon, 31 Dec 2012 09:51:19 +0000 The aim of the study was to investigate the association between elevated serum fetuin-A and increased urine albumin excretion in obese rats, and whether increased urine albumin excretion was modified by improving hepatic steatosis and lipid metabolism disorder. Male Wistar rats 4 weeks in age were randomly divided into three groups and fed with normal chow (control group), high-fat chow (obesity group), or high-fat chow plus fenofibrate (fenofibrate group). After 24 weeks, both body weight and visceral fat/body weight ratio in obese rats were higher than in controls. A difference in serology markers and pathology associated with hepatic steatosis was also found among the three groups. Serum fetuin-A and the expression of NF-κB in the liver were increased, while serum adiponectin was decreased in obese rats in comparison to controls (). Urinary albumin/creatinine ratio (ACR) was increased in the obesity group compared to controls (). The fenofibrate intervention reduced serum fetuin-A and NF-κB expression in the liver and increased serum adiponectin compared to obese rats and was accompanied by decrease in ACR. A positive correlation was found between ACR and fetuin-A (, ), and a negative correlation was found between ACR and adiponectin (, ). We conclude that elevated fetuin-A levels are associated with microalbuminuria in obese rats, and abnormal albuminuria is reversible by improving hepatic steatosis. Yanyan Li, Xiaodong Sun, and Yerong Yu Copyright © 2013 Yanyan Li et al. All rights reserved. Lipoprotein(a) in Cardiovascular Diseases Sun, 30 Dec 2012 14:57:25 +0000 Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events. Michele Malaguarnera, Marco Vacante, Cristina Russo, Giulia Malaguarnera, Tijana Antic, Lucia Malaguarnera, Rita Bella, Giovanni Pennisi, Fabio Galvano, and Alessandro Frigiola Copyright © 2013 Michele Malaguarnera et al. All rights reserved. Sabiporide Reduces Ischemia-Induced Arrhythmias and Myocardial Infarction and Attenuates ERK Phosphorylation and iNOS Induction in Rats Sun, 30 Dec 2012 10:53:16 +0000 The aim of the present study was to investigate the effects of sabiporide, a potent and selective NHE1 inhibitor, on myocardial ischemia-induced arrhythmias and myocardial infarction and the possible pathways related to the cardioprotection afforded by sabiporide treatment. Anesthetized rats were subjected to myocardial ischemia via left main coronary artery occlusion for 30 minutes, followed by 2 hours of reperfusion. Administration of sabiporide (0.01–3.0 mg/kg) prior to coronary artery occlusion dose-dependently reduced ischemia-induced arrhythmias and infarct size with an ED50 value of 0.14 mg/kg. Administration of sabiporide (1.0 mg/kg) prior to reperfusion also reduced infarct size by 38.6%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase and troponin I. In addition, sabiporide (1.0 mg/kg) given prior to coronary artery occlusion or immediately before reperfusion significantly reduced phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and the expression of the inducible nitric oxide synthase (iNOS) following myocardial ischemia-reperfusion. This study demonstrates that sabiporide is a potent and effective cardioprotective agent during myocardial ischemia and reperfusion, by reducing serious ventricular arrhythmias and myocardial infarct size. The cardioprotection afforded by sabiporide is attributed in part to inhibition of ERK1/2 phosphorylation and suppression of iNOS expression. Henri Doods and Dongmei Wu Copyright © 2013 Henri Doods and Dongmei Wu. All rights reserved. High Insulin and Leptin Increase Resistin and Inflammatory Cytokine Production from Human Mononuclear Cells Mon, 24 Dec 2012 07:38:56 +0000 Resistin and the proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF-α, IL-6, and IL-1β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF-α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1β production. By comparison, exposure to dexamethasone reduced TNF-α, IL-6, and IL-1β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-α, IL-6, and IL-1β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients. Panayoula C. Tsiotra, Eleni Boutati, George Dimitriadis, and Sotirios A. Raptis Copyright © 2013 Panayoula C. Tsiotra et al. All rights reserved. A Retrospective Longitudinal Cohort Study of Antihypertensive Drug Use and New-Onset Diabetes in Taiwanese Patients Sun, 23 Dec 2012 07:42:07 +0000 Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined in a clinical setting. The aim was to investigate the association between antihypertensive drugs and NOD in Taiwan. We conducted a retrospective study of hypertensive Taiwanese patients receiving antihypertensive drugs treatment between January 2006 and December 2011. Clinical information and laboratory parameters were collected by reviewing the medical records. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 120 NOD cases were identified in 1001 hypertensive patients during the study period. The risk of NOD after adjusting sex, age, baseline characteristics, and lipid profiles was higher among users of thiazide diuretics (OR, 1.65; 95% confidence interval (CI), 1.12–2.45) and nondihydropyridine (non-DHP) calcium channel blockers (CCBs) (OR, 1.96; 95% CI, 1.01–3.75) than among nonusers. Other antihypertensive drug classes were not associated with risk of NOD. Our results show that patients with hypertension who take thiazide diuretics and non-DHP CCBs are at higher risk of developing NOD than those who take other classes of antihypertensive drugs in Taiwan. Ching-Ya Huang, Tsochiang Ma, Liyun Tien, Yow-Wen Hsieh, Shwu-Yi Lee, Hung-Yi Chen, and Gwo-Ping Jong Copyright © 2013 Ching-Ya Huang et al. All rights reserved. Association between Polymorphisms of Alpha-Adducin Gene and Essential Hypertension in Chinese Population Thu, 20 Dec 2012 15:23:42 +0000 The association between polymorphisms of α-adducin (ADD1) gene and essential hypertension is still unclear. Thus, we carried out a case-control study and an interaction analysis to test whether ADD1 is a common candidate gene for hypertension in the Chinese population. Blood samples and information including body mass index (BMI), smoking habit, and alcohol abuse were collected. Meanwhile, total cholesterol, high density lipoprotein, triglyceride were measured by automatic biochemistry analyzer. All 6 tag single nucleotide polymorphisms (tagSNPs) within ADD1 gene were genotyped by SNPstream genotyping system. Multifactor dimensionality reduction (MDR) was used to identify the interactions among the SNPs and the non-genetic factors. Results showed that plasma triglyceride, total cholesterol, and BMI were significantly higher in the hypertensive group than in the control group. Result from genotyping indicated that rs4963 was significantly associated with essential hypertension. After stratification by gender, rs4963 was associated with essential hypertension only in males. MDR analysis indicated that interaction among BMI, rs4963, and rs16843452 were involved in susceptibility of hypertension. The present study indicated that rs4963 within ADD1 gene was associated with essential hypertension in Chinese population, which might be related to altered exonic splicing and disrupted gene regulation. Li-na Zhang, Lin-dan Ji, Li-juan Fei, Fang Yuan, Yue-miao Zhang, and Jin Xu Copyright © 2013 Li-na Zhang et al. All rights reserved. Desipramine Pretreatment Improves Sympathetic Remodeling and Ventricular Fibrillation Threshold after Myocardial Ischemia Wed, 03 Oct 2012 09:55:06 +0000 Abnormal increase in sympathetic nerve sprouting was responsible for the ventricular arrhythmogenesis after myocardial infarction. This study investigated whether the norepinephrine transporter inhibitor, desipramine, can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) after myocardial ischemia-reperfusion. Rats were administered desipramine (0.8 mg/kg, IV) before or after myocardial ischemia. VFT, infarct size, tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43)-positive nerve fibers were measured after one week. The VFT of preischemic treatment group was 11.0±2.65 V and significantly higher than that of control ischemic group (7.2±1.30 V, 𝑃<0.05). Infarct size in the preischemic treatment group (23.3±2.4%) was significantly lower than that in the control ischemic group (30.8±1.3%, 𝑃<0.05) and the delayed application group (27.1±2.6%, 𝑃<0.05). The density of TH and GAP43-positive nerve fibers in the control ischemic group was significantly higher than that in the other three groups (𝑃<0.05). The density of nerve fibers improved after desipramine treatment. Moreover, there was a negative correlation between the VFT and both TH and GAP43-positive nerve fiber density in the infarct border zone (𝑃<0.05). Desipramine treatment before acute myocardial ischemia can decrease infarct size, improve sympathetic remodeling, and increase VFT and electrical stability of ischemic hearts. Desipramine appears to cause myocardial ischemic preconditioning. Xiaolin Wu, Hong Jiang, Lilei Yu, Xiaorong Hu, and Wenwei Liu Copyright © 2012 Xiaolin Wu et al. All rights reserved. Associations of Polymorphisms in the Apolipoprotein APOA1-C3-A5 Gene Cluster with Acute Coronary Syndrome Wed, 23 May 2012 10:37:01 +0000 Background. Acute coronary syndromes (ACSs) are clinically cardiovascular events associated with dyslipidemia in common. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A5 gene cluster are associated with diabetes and familial combined hyperlipidaemia (FCH). Little is known about whether the polymorphisms in these genes affect lipid homeostasis in patients with ACSs. The present paper aimed to examine these associations with 4 SNPs in the APOA1 −75G>A, the APOC3 −455T>C, and APOA5 −1131T>C, c.553G>T variant to ACSs in Chinese Han. Methods. Chinese Han of 229 patients with ACSs and 254 unrelated controls were analyzed. Four SNPs in APOA1/C3/A5 cluster were genotyped and lipid was determined. Results. Our data show that minor allelic frequencies of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>T polymorphisms in patients with ACSs were significantly higher than control group (𝑃<0.05). Furthermore, the 3 polymorphic sites were strongly of linkage disequilibrium, and minor alleles of 3 SNP sites had higher TG level than wild alleles (𝑃<0.05), APOC3 −455C and APOA5 c.553T allele carriers also had lower level of HDL-C. Conclusions. The minor alleles of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>T polymorphisms are closely associated with ACSs. Yan Ding, Ming An Zhu, Zhi Xiao Wang, Jing Zhu, Jing Bo Feng, and Dong Sheng Li Copyright © 2012 Yan Ding et al. All rights reserved. Exogenous High-Mobility Group Box 1 Protein Injection Improves Cardiac Function after Myocardial Infarction: Involvement of Wnt Signaling Activation Mon, 21 May 2012 09:20:02 +0000 Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and β-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (𝑃<0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (𝑃<0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and β-catenin proteins (𝑃<0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/β-catenin signaling activation. Xiaoya Zhou, Xiaorong Hu, Jing Xie, Changwu Xu, Weipan Xu, and Hong Jiang Copyright © 2012 Xiaoya Zhou et al. All rights reserved. AngiotensinII Preconditioning Promotes Angiogenesis In Vitro via ERKs Phosphorylation Tue, 28 Feb 2012 08:06:32 +0000 AngiotensinII (AngII) is involved in not only the formation of cardiac hypertrophy but also the development of cardiac remodeling both of which are associated with myocardial angiogenesis. This study was therefore performed to clarify the effects of AngII on the formation of vasculatures by cultured cardiac microvascular endothelial cells (CMVECs) after a long-period stimulation with or without the AngII preconditioning. Incubation with AngII for 18 hrs significantly impaired the formation of capillary-like tubes comparing to that without AngII. CMVECs with AngII pretreatment for 5 and 10 min formed more capillary-like tubes than those without AngII pretreatment, suggesting that preconditioning with AngII at a lower dose for a short period could prevent the further damage of CMVECs by a higher concentration of AngII. Moreover, AngII (10−7 M) stimulation for 5 and 10 min significantly induced the increase in extracellular signal-regulated protein kinases (ERKs) phosphorylation, and an ERKs inhibitor, PD98059, abrogated the increase in the formation of capillary-like tubes induced by the AngII-pretreatment. In conclusion, preconditioning with a lower concentration of AngII for a short period prevents the subsequent impairment of CMVECs by a higher dose of AngII, at least in part, through the increase in ERKs phosphorylation. Aili Guan, Yunzeng Zou, Hui Gong, Yuhong Niu, Yong Ye, Jianguo Jia, Bingyu Li, Guoping Zhang, Sanli Qian, and Junbo Ge Copyright © 2012 Aili Guan et al. All rights reserved. Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats Sun, 16 Oct 2011 17:22:29 +0000 Diabetes mellitus is associated with decreased NO bioavailability in the myocardium. Ginsenoside Rb1 has been shown to confer cardioprotection against ischemia reperfusion injury. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing eNOS expression in the myocardium. The myocardial I/R injury were induced by occluding the left anterior descending artery for 30 min followed by 120 min reperfusion. An eNOS inhibitor L-NAME or Rb1 were respectively administered 25 min or 10 min before inducing ischemia. Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group. Ginsenoside Rb1 induced myocardial protection was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH (). Moreover, the myocardial oxidative stress and tissue histological damage was attenuated by Ginsenoside Rb1 (). L-NAME abolished the protective effects of Ginsenoside Rb1. It is concluded that Ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress. Rui Xia, Bo Zhao, Yang Wu, Jia-Bao Hou, Li Zhang, Jin-Jin Xu, and Zhong-Yuan Xia Copyright © 2011 Rui Xia et al. All rights reserved. Histamine Blood Concentration in Ischemic Heart Disease Patients Mon, 06 Jun 2011 16:32:26 +0000 The aim of this study was to investigate histamine blood concentration in subjects suffering from different types of ischemic heart diseases during the period of eight days. Our results showed that the histamine blood level was associated with different types of ischemic heart diseases. The blood histamine level in all investigated patients was significantly higher when compared to control subjects (44.87 ± 1.09 ng mL−1), indicating the increase of histamine release in patients suffering from coronary diseases. In patients suffering from ACS-UA and ACS-STEMI, the second day peak of histamine level occurs (90.85 ± 6.34 ng mL−1 and 121.7 ± 6.34 ng mL−1, resp.) probably as the reperfusion event. Furthermore, our data suggest that histamine can be additional parameter of myocardial ischemia along with cardiac specific enzymes and may prove to be an excellent single prognostic marker for multitude of ischemic heart diseases. Vladimir Zdravkovic, Suzana Pantovic, Gvozden Rosic, Aleksandra Tomic-Lucic, Nemanja Zdravkovic, Maja Colic, Zdravko Obradovic, and Mirko Rosic Copyright © 2011 Vladimir Zdravkovic et al. All rights reserved. Characterization for Binding Complex Formation with Site-Directly Immobilized Antibodies Enhancing Detection Capability of Cardiac Troponin I Tue, 29 Sep 2009 15:57:19 +0000 The enhanced analytical performances of immunoassays that employed site-directly immobilized antibodies as the capture binders have been functionally characterized in terms of antigen-antibody complex formation on solid surfaces. Three antibody species specific to cardiac troponin I, immunoglobulin G (IgG), Fab, and F were site-directly biotinylated within the hinge region and then immobilized via a streptavidin-biotin linkage. The new binders were more efficient capture antibodies in the immunoassays compared to randomly bound IgG, particularly, in the low antibody density range. The observed improvements could have resulted from controlled molecular orientation and also from flexibility, offering conditions suitable for binding complex formations. Il-Hoon Cho, Sung-Min Seo, Jin-Woo Jeon, and Se-Hwan Paek Copyright © 2009 Il-Hoon Cho et al. All rights reserved.