BioMed Research International: Vascular Medicine http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Epithelial-Mesenchymal Transition Regulated by EphA2 Contributes to Vasculogenic Mimicry Formation of Head and Neck Squamous Cell Carcinoma Thu, 17 Apr 2014 13:34:19 +0000 http://www.hindawi.com/journals/bmri/2014/803914/ Purpose. Vasculogenic mimicry (VM) was related to invasion and metastasis of head and neck squamous cell carcinoma (HNSCC) patients. This study was designed to investigate the role of EphA2 in VM formation of HNSCC. Methods. The SiRNA technique was used to knock down the expression of EphA2 in vitro. The ability of cell migration and invasion were measured by transwell and wound healing assays; three-dimensional culture was used to detect the ability of channel-like structure formation; Western blot was used to detect the expression of epithelial-mesenchymal transition- (EMT-) related molecules in vitro. Further semiquantitative real-time RT-PCR assays and immunohistochemistry were used to demonstrate expression of EphA2 and EMT-related molecules according to VM presence or not in human tissue. Results. Knocking down EphA2 in vitro leads to disabled channel-like structure formation, reduction of invasion and migration ability, and reverse of EMT-related markers. Both semiquantitative real-time RT-PCR and immunohistochemistry showed that expressions of EphA2, Twist, and Vimentin were higher in the VM-positive group than in the VM-negative group significantly, while expressions of E-cadherin, claudin4, and DSG-3 were reverse. Conclusions. EphA2 played a key role in VM formation of HNSCC through regulation of EMT. Wei Wang, Peng Lin, Baocun Sun, Shiwu Zhang, Wenjuan Cai, Chunrong Han, Li Li, Honghua Lu, and Xiulan Zhao Copyright © 2014 Wei Wang et al. All rights reserved. Scattering Coefficients of Mice Organs Categorized Pathologically by Spectral Domain Optical Coherence Tomography Sun, 13 Apr 2014 15:21:51 +0000 http://www.hindawi.com/journals/bmri/2014/471082/ Differences in tissue density cause a variety of scattering coefficients. To quantify optical coherence tomography (OCT) images for diagnosis, the tissue's scattering coefficient is estimated by curve fitting the OCT signals to a confocal single backscattering mode. The results from a group of 30 mice show that the scattering coefficients of bone, skin, liver, brain, testis, and spleen can be categorized into three groups: a scattering coefficient between 1.947 and 2.134 mm−1: bone and skin; a scattering coefficient between 1.303 and 1.461 mm−1: liver and brain; a scattering coefficient between 0.523 and 0.634 mm−1: testis and spleen. The results indicate that the scattering coefficient is tissue specific and could be used in tissue diagnosis. Q. Q. Zhang, X. J. Wu, C. Wang, S. W. Zhu, Y. L. Wang, Bruce Z. Gao, and X.-C. Yuan Copyright © 2014 Q. Q. Zhang et al. All rights reserved. The Evolution of Cardiovascular Surgery in Elderly Patient: A Review of Current Options and Outcomes Thu, 10 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/736298/ Due to the increase in average life expectancy and the higher incidence of cardiovascular disease with advancing age, more elderly patients present for cardiac surgery nowadays. Advances in pre- and postoperative care have led to the possibility that an increasing number of elderly patients can be operated on safely and with a satisfactory outcome. Currently, coronary artery bypass surgery, aortic and mitral valve surgery, and major surgery of the aorta are performed in elderly patients. The data available show that most cardiac surgical procedures can be performed in elderly patients with a satisfactory outcome. Nevertheless, the risk for these patients is only acceptable in the absence of comorbidities. In particular, renal dysfunction, cerebrovascular disease, and poor clinical state are associated with a worse outcome in elderly patients. Careful patient selection, flawless surgery, meticulous hemostasis, perfect anesthesia, and adequate myocardial protection are basic requirements for the success of cardiac surgery in elderly patients. The care of elderly cardiac surgical patients can be improved only through the strict collaboration of geriatricians, anesthesiologists, cardiologists, and cardiac surgeons, in order to obtain a tailored treatment for each individual patient. Francesco Nicolini, Andrea Agostinelli, Antonella Vezzani, Tullio Manca, Filippo Benassi, Alberto Molardi, and Tiziano Gherli Copyright © 2014 Francesco Nicolini et al. All rights reserved. Engineered Tumor Cell Apoptosis Monitoring Method Based on Dynamic Laser Tweezers Tue, 01 Apr 2014 12:30:53 +0000 http://www.hindawi.com/journals/bmri/2014/279408/ Monitoring the cells’ apoptosis progression could provide a valuable insight into the temporal events that initiate cell death as well as the potential for rescue of apoptotic cells. In this paper, we engineered a novel and robust method for monitoring apoptosis of tumor cells based on dynamic laser tweezers, using A549 and HeLa cell line as typical samples. The entire experiment can be completed in a few hours with small amount of fluid sample, presenting great advantages of celerity, microscaled measurement, and label-free explorations without perturbing experimental conditions in combination with other probes. Validity and stability of this method are verified experimentally in terms of physical parameters of the system. The proposed technique has great potential in improving cancer treatment by monitoring the objective efficacy of tumor cell killing. Yuquan Zhang, Xiaojing Wu, Changjun Min, Siwei Zhu, H. Paul Urbach, and Xiaocong Yuan Copyright © 2014 Yuquan Zhang et al. All rights reserved. An Experimental Study to Replace the Thoracic Descending Aorta for Pigs with a Self-Made Sutureless Blood Vessel Tue, 18 Feb 2014 11:38:49 +0000 http://www.hindawi.com/journals/bmri/2014/587393/ To simplify the procedure of blood vessel replacement operation and shorten the vascular anastomosis time, we developed a special artificial blood vessel which can be connected to native blood vessels without suture. The self-made sutureless blood vessel (SMSBV) was made from two titanium connectors and a Gore-Tex graft. To investigate blood compatibility and histocompatibility of the SMSBV, we carried thoracic descending aorta replacement using either SMSBV or Gore-Tex, respectively, in pigs. The aortic clamp time and the operative blood loss in the experimental group (using SMSBV) were less than those in the control group (using Gore-Tex). The whole blood hematocrit, platelet count, plasma soluble P-selectin, plasma free hemoglobin, and interleukins 2, 6 at each time point were not different significantly between the two groups. Light microscopy and transmission electron microscopy examination showed there were layers of vascular smooth muscle cells and endothelial cells adhered in the inner wall of artificial blood vessel without any signs of thrombosis. Based on the result, we have drawn the conclusion that the application of SMSBV can significantly shorten the vascular anastomosis time, reduce operative blood loss, and show good blood and tissue compatibility. Fenglin Song, Wenwu Zhou, Tao Tang, Xiaobing Li, Xiaoming Wu, and Jinfu Yang Copyright © 2014 Fenglin Song et al. All rights reserved. Comparison of Semi-Automated and Manual Measurements of Carotid Intima-Media Thickening Tue, 21 Jan 2014 12:09:10 +0000 http://www.hindawi.com/journals/bmri/2014/531389/ Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and atherosclerotic risks. Technological advances have semiautomated CIMT image acquisition and quantification. Studies comparing manual and automated methods have yielded conflicting results possibly due to plaque inclusion in measurements. Low atherosclerotic risk subjects were recruited to minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK) images of the common carotid artery using both manual and semiautomated methods (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean differences of paired measurements (Bland-Altman method) were used to compare both methodologies. The ICC of manual ( mm) and automated (0.524 ± 0.068 mm) methods was and an absolute mean bias ± SD of  mm was observed. Interobserver and intraobserver ICC were greater for automated ( and 0.99) compared to manual ( and 0.88) methods. Although not considered to be clinically significant, manual measurements yielded higher values compared to automated measurements. Automated measurements were more reproducible and showed lower interobserver variation compared to manual measurements. These results offer important considerations for large epidemiological studies. Oscar Mac Ananey, Greg Mellotte, and Vincent Maher Copyright © 2014 Oscar Mac Ananey et al. All rights reserved. Roles of Bone-Marrow-Derived Cells and Inflammatory Cytokines in Neointimal Hyperplasia after Vascular Injury Tue, 14 Jan 2014 09:26:00 +0000 http://www.hindawi.com/journals/bmri/2014/945127/ Bone-marrow-derived cells can generate vascular progenitor cells that contribute to pathological remodeling in models of restenosis after percutaneous coronary intervention (PCI). We created models of vascular injury in mice with bone marrow transplants (BMT) to determine relationships between bone-marrow-derived cells and subsequent biological factors. Mesenchymal stromal cells (MSCs) seemed to inhibit the inflammatory reaction and help stabilize injured vascular regions through mobilizing more endogenous bone-marrow-derived (EBMD) cells to the peripheral circulation. Granulocyte-colony stimulating factor (G-CSF) mobilized more EBMD cells to the peripheral circulation, and they accumulated on the injured side of the vascular lumen. The inflammatory cytokines, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 mobilized EBMD cells that play an important role in the process of neointimal hyperplasia after vascular injury. These factors might comprise a mechanism that alters the transdifferentiation or paracrine capabilities of EBMD cells and are potential targets of treatment for patients with cardiovascular diseases. Makoto Shoji, Shinji Koba, and Youichi Kobayashi Copyright © 2014 Makoto Shoji et al. All rights reserved. Impact of Mean Platelet Volume on Combined Safety Endpoint and Vascular and Bleeding Complications following Percutaneous Transfemoral Transcatheter Aortic Valve Implantation Mon, 23 Dec 2013 18:13:15 +0000 http://www.hindawi.com/journals/bmri/2013/645265/ Background. Vascular and bleeding complications remain important complications in patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI). Platelets play an important role in bleeding events. Mean platelet volume (MPV) is an indicator of platelet activation. The objective of this study was to assess whether low MPV is an indicator of major vascular and bleeding complications following TF-TAVI. Methods. A retrospective cohort study of 330 subjects undergoing TF-TAVI implantation was performed. The primary study endpoint was the occurrence of combined safety endpoint (CSEP); secondary endpoints included major vascular complications and life-threatening bleeding. Endpoints were defined according to Valve Academic Research Consortium 2. Results. The CSEP at 30 days was reached in 30.9%; major vascular complications were observed in 14.9% while life-threatening bleeding occurred in 20.6%. Logistic Euroscore and MPV were independent predictors of CSEP. Predictors of vascular complications were female sex, previous myocardial infarction, red blood cell distribution width (RDW), and MPV while predictors of life-threatening bleeding were peripheral arterial disease, RDW, and MPV. Conclusion. A low baseline MPV was shown for the first time to be a significant predictor of CSEP, major vascular complications, and life-threatening bleeding following TF-TAVI. Caroline J. Magri, Alaide Chieffo, Alessandro Durante, Azeem Latib, Matteo Montorfano, Francesco Maisano, Michela Cioni, Eustachio Agricola, Remo Daniel Covello, Chiara Gerli, Annalisa Franco, Pietro Spagnolo, Ottavio Alfieri, and Antonio Colombo Copyright © 2013 Caroline J. Magri et al. All rights reserved. Alleviation of Hyperglycemia Induced Vascular Endothelial Injury by Exenatide Might Be Related to the Reduction of Nitrooxidative Stress Tue, 26 Nov 2013 10:19:58 +0000 http://www.hindawi.com/journals/bmri/2013/843657/ We will investigate the effects of exenatide on vascular endothelial injury and nitrooxidative stress in hyperglycemia both in vivo and in vitro and explore the role of nitrooxidative stress in endothelium-protective action of exenatide. Healthy male Wistar rats were randomly divided into 4 groups: control, diabetes mellitus (DM) model, low dose of exenatide treatment, and high dose of exenatide treatment. In vitro study showed that, compared with control group, the DM rats exhibited a lowered endothelium-dependent relaxation and damaged structural integrity of thoracic aortas, and there was a significant increase in plasma nitrotyrosine concentration. These parameters were improved after treatment with either low dose or high dose of exenatide for 45 days. In vitro study showed that exendin-4 (the active ingredient of exenatide) attenuated HUVECs injury induced by high glucose, with improving cell viability and attenuating cell apoptosis. Exendin-4 also significantly alleviated the increased malondialdehyde (MDA), nitrotyrosine content, and inducible nitric oxide synthase (iNOS) expression induced by high glucose in HUVECs. In conclusion, this study demonstrates that exenatide treatment can alleviate the vascular endothelial injury, as well as attenuating the nitrooxidative stress in hyperglycemia, implying that the endothelium-protective effect of exenatide might be related to the reduction of nitrooxidative stress. Qian Zhao, Chun-ling Xu, Hai-yan Xiong, Wen Huang, Mei Zhang, Yun Wang, Si-yu Wang, and Wen Wang Copyright © 2013 Qian Zhao et al. All rights reserved. Clinical Application of Vascular Regenerative Therapy for Peripheral Artery Disease Sun, 24 Nov 2013 09:16:06 +0000 http://www.hindawi.com/journals/bmri/2013/179730/ Prognosis of peripheral artery disease (PAD), especially critical limb ischemia, is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in leg amputation and, therefore, vascular regenerative therapy is expected in this field. Gene therapy using vascular endothelial growth factor is the first step of vascular regenerative therapy, but did not confirm effectiveness in a large-scale randomized comparative study. Based on animal experiments, bone marrow mononuclear cells (MNCs), peripheral blood MNCs were used as the cell source for regenerative therapy. Those cells were confirmed to be effective to decrease rest pain and ulcer size, but its effect was not fully satisfied. Mesenchymal stem cells (MSCs) are expected as an effective cell source for vascular regeneration and clinical studies are ongoing, because the cells are able to differentiate into various cell types and produce a significant amount of vascular growth factors. Of vascular regeneration therapy, peripheral MNCs and bone marrow MNCs were recognized as advanced medical technology but do not attain to the standard therapy. However, clinical use of MSCs have already started, and induced pluripotent stem cells are surely promising tool for vascular regeneration therapy although further basic studies are required for clinical application. Hiroshi Suzuki and Yoshitaka Iso Copyright © 2013 Hiroshi Suzuki and Yoshitaka Iso. All rights reserved. CX3CR1 Receptor Polymorphisms, Th1 Cell Recruitment, and Acute Myocardial Infarction Outcome: Looking for a Link Thu, 07 Nov 2013 08:50:18 +0000 http://www.hindawi.com/journals/bmri/2013/451349/ Fractalkine is a proinflammatory chemokine that participates in atherosclerotic process mediating the interactions of vascular cells and leukocytes and selective recruitment of Th1 lymphocytes, through interaction with CX3CR1 receptor. The polymorphism of the fractalkine receptor 280M-containing haplotype, which codifies for a receptor with minor expression and with a reduced binding capability, represents a novel protective factor of atherosclerotic disease. We investigated the association among CX3CR1 genotype, the inflammatory infiltrate subpopulations recruited in the plaque, and the in situ expression of fractalkine and its receptor, in patients who died of myocardial infarction (AMI) compared with subjects who died of noncardiac causes. Patients with nonlethal AMI (AMI survivors) were also investigated to correlate the CX3CR1 polymorphisms and the incidence of lethal AMI. A strong T cells infiltrate was found in infarct related artery (IRA) plaques of AMI patients presenting the V249 T280 haplotype (84%). Conversely, a decreased T cell recruitment was associated with I249T280 haplotype in the controls (64%). The significant higher presence of the variant allele I249 in homo- and heterozygosis, found in controls (91%) and in AMI survivors (94%), with respect to the patients who died of AMI (48%), showed the relevance of this polymorphism both in the onset and outcome of acute myocardial infarction. The presence of CX3CR1 polymorphisms could influence the incidence and the outcome of acute myocardial infarction, altering the inflammation of the whole coronary tree by the impaired recruitment of Th1 polarized subpopulation in the coronary plaque. S. Pucci, P. Mazzarelli, M. J. Zonetti, T. Fisco, E. Bonanno, L. G. Spagnoli, and A. Mauriello Copyright © 2013 S. Pucci et al. All rights reserved. Isolation, Characterization, and Transplantation of Cardiac Endothelial Cells Sun, 27 Oct 2013 15:04:51 +0000 http://www.hindawi.com/journals/bmri/2013/359412/ Isolation and ex vivo expansion of cardiac endothelial cells have been a recurrent challenge due to difficulties in isolation, cell heterogeneity, lack of specific markers to identify myocardial endothelial cells, and inadequate conditions to maintain long-term cultures. Herein, we developed a method for isolation, characterization, and expansion of cardiac endothelial cells applicable to study endothelial cell biology and clinical applications such as neoangiogenesis. First, we dissociated the cells from murine heart by mechanical disaggregation and enzymatic digestion. Then, we used flow cytometry coupled with specific markers to isolate endothelial cells from murine hearts. CD45+ cells were gated out to eliminate the hematopoietic cells. CD31+/Sca-1+ cells were isolated as endothelial cells. Cells isolated from atrium grew faster than those from ventricle. Cardiac endothelial cells maintain endothelial cell function such as vascular tube formation and acetylated-LDL uptake in vitro. Finally, cardiac endothelial cells formed microvessels in dorsal matrigel plug and engrafted in cardiac microvessels following intravenous and intra-arterial injections. In conclusion, our multicolor flow cytometry method is an effective method to analyze and purify endothelial cells from murine heart, which in turn can be ex vivo expanded to study the biology of endothelial cells or for clinical applications such as therapeutic angiogenesis. Busadee Pratumvinit, Kanit Reesukumal, Kajohnkiart Janebodin, Nicholas Ieronimakis, and Morayma Reyes Copyright © 2013 Busadee Pratumvinit et al. All rights reserved. Paired Measurements of Paraoxonase 1 and Serum Amyloid A as Useful Disease Markers Tue, 22 Oct 2013 14:31:09 +0000 http://www.hindawi.com/journals/bmri/2013/481437/ Paraoxonase 1 (PON1) and serum amyloid A (SAA) are proteins carried by high-density lipoprotein (HDL) particles. Among the HDL-associated protein molecules, SAA, an inflammation-related marker, and PON1, an antioxidant marker, tend to change in relatively clear opposite directions in physiological situations. In clinical chemistry, paired measurements of both markers may provide useful information to understand dysfunctional HDL in diseases with inflammation and oxidative stress conditions. Actually, limited clinical studies have suggested that the combined use of PON1 and SAA may be a tool for observing the pathophysiology of some disease entities. From the findings of experimental studies, PON1 appears to be cooperatively regulated by inflammation- and oxidative stress-related molecules linked with SAA regulation in humans. More studies remain to be performed to ascertain the value of paired measurements of both promising markers in clinical practice. Kazuhiko Kotani, Toshiyuki Yamada, and Alejandro Gugliucci Copyright © 2013 Kazuhiko Kotani et al. All rights reserved. Prevention of Atherosclerosis Progression by 9-cis-β-Carotene Rich Alga Dunaliella in apoE-Deficient Mice Mon, 23 Sep 2013 08:23:13 +0000 http://www.hindawi.com/journals/bmri/2013/169517/ Introduction. β-Carotene-rich diet has been shown to be inversely associated with the risk of coronary heart disease. However, clinical trials using synthetic all-trans-β-carotene failed to demonstrate a beneficial effect. We therefore sought to study the effect of natural source of β-carotene, the alga Dunaliella, containing both all-trans and 9-cis-β-carotene on atherosclerosis. In a previous study we showed that 9-cis-β-carotene-rich powder of the alga Dunaliella inhibits early atherogenesis in low-density lipoprotein receptor knockout mice. Aims. The aims of the current work were to study whether diet enriched with Dunaliella powder would inhibit the progression of established atherosclerosis in old male apoE-deficient mice and to compare the effect of Dunaliella on lipid profile and atherosclerosis in a low-versus high-fat diet fed mice. Methods. In the first experiment, young mice (12 weeks old) were allocated into 3 groups: (1) low-fat diet; (2) low-fat diet + Dunaliella powder (8%); (3) low-fat diet + β-carotene-deficient Dunaliella. In the second experiment, old mice (7 months old) with established atherosclerotic lesions were allocated into 4 groups: (1) low-fat diet; (2) low-fat diet + Dunaliella; (3) high fat-diet; (4) high-fat diet + Dunaliella. Results. In young mice fed a low-fat diet, a trend toward lower atherosclerotic lesion area in the aortic sinus was found in the Dunaliella group compared with the control group. In old mice with established atherosclerotic lesion, Dunaliella inhibited significantly plasma cholesterol elevation and atherosclerosis progression in mice fed a high-fat diet. Conclusion. The results of this study suggest that a diet containing natural carotenoids, rich in 9-cis-β-carotene, has the potential to inhibit atherosclerosis progression, particularly in high-fat diet regime. Ayelet Harari, Revital Abecassis, Noa Relevi, Zohar Levi, Ami Ben-Amotz, Yehuda Kamari, Dror Harats, and Aviv Shaish Copyright © 2013 Ayelet Harari et al. All rights reserved. Preexisting High Expression of Matrix Metalloproteinase-2 in Tunica Media of Saphenous Vein Conduits Is Associated with Unfavorable Long-Term Outcomes after Coronary Artery Bypass Grafting Mon, 16 Sep 2013 15:45:35 +0000 http://www.hindawi.com/journals/bmri/2013/730721/ Introduction. Migration of the smooth muscle cells (SMCs) to the tunica media in the saphenous vein (SV) transplants is facilitated by matrix metalloproteinases (MMPs). The aim of this study was to identify any associations between expression of MMP-2 or endogenous tissue inhibitors (TIMP-2 and TIMP-3) in the SV segments and late failure of the SV grafts. Methods. Two hundred consecutive patients with a mean age of 63.1 ± 8.9 years who underwent primary isolated venous CABG were examined. Patients were retrospectively split into two subgroups, with the SV graft disease (SVGD (+); ) or without it (SVGD (−); ). In the SV segments, immunohistochemical analysis of the expression of the MMP-2, TIMP-2, and -3 was performed. Results. In the SVGD (+) patients, tissue expression of MMP-2 was stronger, whereas that of both TIMPs was weaker than in the SVGD (−) patients. In majority of the SV segments obtained from the SVGD (−) individuals, a balance in MMP and TIMP expressions was found, whereas an upregulation of MMP-2 expression was usually noted in the SVGD (+) subjects. Conclusion. The strong expression of MMP-2 accompanied by reduced immunostaining of both TIMPs is associated with the development of the SV graft disease and unfavorable CABG outcomes. Bartlomiej Perek, Agnieszka Malinska, Marcin Misterski, Danuta Ostalska-Nowicka, Maciej Zabel, Anna Perek, and Michal Nowicki Copyright © 2013 Bartlomiej Perek et al. All rights reserved. Incidence and Risk Factors of Early Delirium after Cardiac Surgery Thu, 12 Sep 2013 14:55:30 +0000 http://www.hindawi.com/journals/bmri/2013/323491/ Introduction. The aim of our study was to identify the incidence and risk factors of delirium after cardiac surgery implementing Intensive Care Delirium Screening Checklist (ICDSC). Material and Methods. 87 patients, undergoing cardiac surgery at Vilnius University hospital, were prospectively monitored for postoperative delirium development, during intensive care unit stay. Results. The incidence of postoperative delirium was 13.30%. No statistically relevant preoperative predictors of delirium were found. The duration of surgery was significantly longer in delirium group ( versus hours, ). Patients in delirium group more often had blood product transfusions (1.50 (± 1.57) versus 0.49 (± 0.91) ) and had a higher incidence of low cardiac output syndrome (33.30% versus 3.00%, ); they were significantly longer mechanically ventilated ( versus 8.78 ± 4.77 ()) hours (OR = 1.15 ()) and had twice longer ICU stay ( versus 2.60 ± 1.10 ()) days (OR = 1.91 ()). Conclusions. The incidence of delirium after cardiac surgery was 13.3%. Independent predictors of delirium were duration of postoperative mechanical ventilation and intensive care unit stay. Ieva Norkienė, Donata Ringaitienė, Vilma Kuzminskaitė, and Jūratė Šipylaitė Copyright © 2013 Ieva Norkienė et al. All rights reserved. Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery Thu, 22 Aug 2013 08:18:57 +0000 http://www.hindawi.com/journals/bmri/2013/217026/ Objectives. The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency. Methods. Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10−5 M and 10−6 M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels. Results. At the end of the culture period, neointimal thickness was significantly () dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases. Conclusions. Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis. Vito Mannacio, Luigi Di Tommaso, Anita Antignano, Ettorino Di Tommaso, Paolo Stassano, and Carlo Vosa Copyright © 2013 Vito Mannacio et al. All rights reserved. Knockout of Density-Enhanced Phosphatase-1 Impairs Cerebrovascular Reserve Capacity in an Arteriogenesis Model in Mice Tue, 06 Aug 2013 09:18:49 +0000 http://www.hindawi.com/journals/bmri/2013/802149/ Collateral growth, arteriogenesis, represents a proliferative mechanism involving endothelial cells, smooth muscle cells, and monocytes/macrophages. Here we investigated the role of Density-Enhanced Phosphatase-1 (DEP-1) in arteriogenesis in vivo, a protein-tyrosine-phosphatase that has controversially been discussed with regard to vascular cell biology. Wild-type C57BL/6 mice subjected to permanent left common carotid artery occlusion (CCAO) developed a significant diameter increase in distinct arteries of the circle of Willis, especially in the anterior cerebral artery. Analyzing the impact of loss of DEP-1 function, induction of collateralization was quantified after CCAO and hindlimb femoral artery ligation comparing wild-type and DEP-1−/− mice. Both cerebral collateralization assessed by latex perfusion and peripheral vessel growth in the femoral artery determined by microsphere perfusion and micro-CT analysis were not altered in DEP-1−/− compared to wild-type mice. Cerebrovascular reserve capacity, however, was significantly impaired in DEP-1−/− mice. Cerebrovascular transcriptional analysis of proarteriogenic growth factors and receptors showed specifically reduced transcripts of PDGF-B. SiRNA knockdown of DEP-1 in endothelial cells in vitro also resulted in significant PDGF-B downregulation, providing further evidence for DEP-1 in PDGF-B gene regulation. In summary, our data support the notion of DEP-1 as positive functional regulator in vascular cerebral arteriogenesis, involving differential PDGF-B gene expression. Daniel Hackbusch, André Dülsner, Nora Gatzke, Janine Krüger, Philipp Hillmeister, Stephanie Nagorka, Florian Blaschke, Zully Ritter, Christa Thöne-Reineke, Frank-D. Böhmer, Ivo Buschmann, and Kai Kappert Copyright © 2013 Daniel Hackbusch et al. All rights reserved. Aorta Structural Alterations in Term Neonates: The Role of Birth and Maternal Characteristics Thu, 25 Jul 2013 14:12:12 +0000 http://www.hindawi.com/journals/bmri/2013/459168/ Aim. To evaluate the influence of selected maternal and neonatal characteristics on aorta walls in term, appropriately grown-for-gestational age newborns. Methods. Age, parity, previous abortions, weight, height, body mass index before and after delivery, smoking, and history of hypertension, of diabetes, of cardiovascular diseases, and of dyslipidemia were all assessed in seventy mothers. They delivered 34 males and 36 females healthy term newborns who underwent ultrasound evaluation of the anteroposterior infrarenal abdominal aorta diameter (APAO), biochemical profile (glucose, insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, fibrinogen, and D-dimers homeostasis model assessment [HOMAIR]index), and biometric parameters. Results. APAO was related to newborn length (; ), head circumference (; ), gestational age (, ), HOMA index (; ), and D-dimers (, ). Smoke influenced APAO values (odds ratio: 1.80; confidence interval 95%: 1.05–3.30), as well as diabetes during pregnancy (, ). Maternal height influenced neonatal APAO (, ). Multiple regression analysis outlined neonatal D-dimers as still significantly related to neonatal APAO values. Conclusions. Many maternal and neonatal characteristics could influence aorta structures. Neonatal D-dimers are independently related to APAO. Marco Matteo Ciccone, Pietro Scicchitano, Christian Salerno, Michele Gesualdo, Fara Fornarelli, Annapaola Zito, Lucia Filippucci, Roberta Riccardi, Francesca Cortese, Francesca Pini, Lucia Angrisani, Antonio Di Mauro, Federico Schettini, and Nicola Laforgia Copyright © 2013 Marco Matteo Ciccone et al. All rights reserved. Aortic Dissection Type A in Alpine Skiers Sun, 21 Jul 2013 11:29:07 +0000 http://www.hindawi.com/journals/bmri/2013/192459/ Patients and Methods. 140 patients with aortic dissection type A were admitted for cardiac surgery. Seventy-seven patients experienced their dissection in the winter season (from November to April). We analyzed cases of ascending aortic dissection associated with alpine skiing. Results. In 17 patients we found skiing-related aortic dissections. Skiers were taller (180 (172–200) cm versus 175 (157–191) cm, ) and heavier (90 (68–125) kg versus 80 (45–110) kg, ) than nonskiers. An extension of aortic dissection into the aortic arch, the descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and 69%, respectively, with no significant difference between skiers and nonskiers. Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was true for 5% of nonskiers (). Hospital mortality of skiers was 6% versus 13% in nonskiers (). The skiers live at an altitude of 170 (0–853) m.a.s.l. and experience their dissection at 1602 (1185–3105; ) m.a.s.l. In 82% symptom start was during recreational skiing without any trauma. Conclusion. Skiing associated aortic dissection type A is usually nontraumatic. The persons affected live at low altitudes and practice an outdoor sport at unusual high altitude at cold temperatures. Postoperative outcome is good. Thomas Schachner, Nikolaus Fischler, Julia Dumfarth, Nikolaos Bonaros, Christoph Krapf, Wolfgang Schobersberger, and Michael Grimm Copyright © 2013 Thomas Schachner et al. All rights reserved. Association of Atherosclerotic Peripheral Arterial Disease with Adiponectin Genes SNP+45 and SNP+276: A Case-Control Study Mon, 03 Jun 2013 15:43:19 +0000 http://www.hindawi.com/journals/bmri/2013/501203/ Objectives. We hypothesized that adiponectin gene SNP+45 (rs2241766) and SNP+276 (rs1501299) would be associated with atherosclerotic peripheral arterial disease (PAD). Furthermore, the association between circulating adiponectin levels, fetuin-A, and tumoral necrosis factor-alpha (TNF-) in patients with atherosclerotic peripheral arterial disease was investigated. Method. Several blood parameters (such as adiponectin, fetuin-A, and TNF-) were measured in 346 patients, 226 with atherosclerotic peripheral arterial disease (PAD) and 120 without symptomatic PAD (non-PAD). Two common SNPs of the ADIPOQ gene represented by +45T/G 2 and +276G/T were also investigated. Results. Adiponectin concentrations showed lower circulating levels in the PAD patients compared to non-PAD patients (). Decreasing adiponectin concentration was associated with increasing serum levels of fetuin-A in the PAD patients. None of the investigated adiponectin SNPs proved to be associated with the subjects’ susceptibility to PAD (). Conclusion. The results of our study demonstrated that neither adiponectin SNP+45 nor SNP+276 is associated with the risk of PAD. Claudia D. Gherman, Doru Pamfil, and Sorana D. Bolboacă Copyright © 2013 Claudia D. Gherman et al. All rights reserved. PPAR Agonist GW501516 Inhibits PDGF-Stimulated Pulmonary Arterial Smooth Muscle Cell Function Related to Pathological Vascular Remodeling Wed, 27 Mar 2013 10:43:00 +0000 http://www.hindawi.com/journals/bmri/2013/903947/ Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Growth factors, cytokines, and lipid mediators are involved in this remodeling process. Recent reports suggest that the peroxisome proliferator-activated receptors (PPARs) play important roles in the regulation of cell growth and differentiation as well as tissue wounding and repair. In this study, we examined the role of PPARδ in the regulation of proliferation, migration, collagen synthesis, and chemokine production in human pulmonary arterial smooth muscle cells (HPASMCs). The data showed that PPARδ was the most abundant isoform in HPASMCs. PPARδ was upregulated in HPASMCs treated with PDGF, which is the major mediator in pulmonary vascular remodeling. Activation of PPARδ by GW501516, a specific PPARδ ligand, significantly inhibited PDGF-induced proliferation in HPASMCs. The inhibitory effect of GW501516 on HPASMCs was associated with decreased expression of cyclin D1, cyclin D3, CDK2, and CDK4 as well as increased expression of the cell cycle inhibitory genes G0S2 and . Pretreatment of HPASMCs with GW501516 significantly inhibited PDGF-induced cell migration and collagen synthesis. GW501516 also significantly attenuated TNF-mediated expression of MCP-1. These results suggest that PPARδ may be a potential therapeutic target against the progression of vascular remodeling in PAH. Guangjie Liu, Xuan Li, Yan Li, Xin Tang, Jie Xu, Ran Li, Peng Hao, and Yongchang Sun Copyright © 2013 Guangjie Liu et al. All rights reserved. In Vivo Imaging of Leukocyte Recruitment to the Atheroprone Femoral Artery Reveals Anti-Inflammatory Effects of Rosuvastatin Sun, 30 Dec 2012 16:06:29 +0000 http://www.hindawi.com/journals/bmri/2013/962369/ Objective. To monitor the anti-inflammatory effect of rosuvastatin in leukocyte endothelial interactions in the atheroprone femoral artery in vivo. Methods and Results. Male Apolipoprotein E null mice (ApoE−/− mice, 6 weeks old) were fed a high-fat diet (20% fat, 1.25% cholesterol) with or without the HMG CoA reductase inhibitor rosuvastatin (10 mg/kg/day) for 6 weeks. Significant leukocyte adhesion was observed in the femoral artery of ApoE−/− mice, but not of wild type mice, in the absence of rosuvastatin. Interestingly, no obvious plaque formation was observed in the artery at this time point. The number of adherent leukocytes was dramatically diminished in ApoE−/− mice treated with rosuvastatin. DHE-associated oxidative stress and the expression of gp91-phox, a component of NADPH oxidase, were induced in ApoE−/− mice and were abolished by rosuvastatin treatment. Conclusion. Our data documented leukocyte recruitment prior to lipid accumulation and subsequent inhibition by rosuvastatin. The underlying mechanism seemed to involve oxidative stress and an anti-inflammatory effect on the endothelium of atheroprone vessels. Mizuko Osaka, Sumihiko Hagita, and Masayuki Yoshida Copyright © 2013 Mizuko Osaka et al. All rights reserved. Genistein Attenuates Vascular Endothelial Impairment in Ovariectomized Hyperhomocysteinemic Rats Tue, 06 Nov 2012 13:19:33 +0000 http://www.hindawi.com/journals/bmri/2012/730462/ Hyperhomocysteinemia (HHcy) is a well-known independent risk factor for vascular diseases in the general population. This study was to explore the effect of genistein (GST), a natural bioactive compound derived from legumes, on HHcy-induced vascular endothelial impairment in ovariectomized rats in vivo. Thirty-two adult female Wistar rats were assigned randomly into four groups (): (a) Con: control; (b) Met: 2.5% methionine diet; (c) OVX + Met: ovariectomy + 2.5% methionine diet; (d) OVX + Met + GST: ovariectomy + 2.5% methionine diet + supplementation with genistein. After 12 wk of different treatment, the rats' blood, toracic aortas and liver samples were collected for analysis. Results showed that high-methionine diet induced both elevation of plasma Hcy and endothelial dysfunction, and ovariectomy deteriorated these injuries. Significant improvement of both functional and morphological changes of vascular endothelium was observed in OVX + Met + GST group; meanwhile the plasma Hcy levels decreased remarkably. There were significant elevations of plasma ET-1 and liver MDA levels in ovariectomized HHcy rats, and supplementation with genistein could attenuate these changes. These results implied that genistein could lower the elevated Hcy levels, and prevent the development of endothelial impairment in ovariectomized HHcy rats. This finding may shed a novel light on the anti-atherogenic activities of genistein in HHcy patients. Panpan Zhen, Qian Zhao, Dandan Hou, Teng Liu, Dongqiao Jiang, Jinhong Duan, Lingqiao Lu, and Wen Wang Copyright © 2012 Panpan Zhen et al. All rights reserved. Validation of a New Animal Model of Vulnerable Plaques by Intravascular Optical Coherence Tomography In Vivo Wed, 03 Oct 2012 10:18:18 +0000 http://www.hindawi.com/journals/bmri/2012/469726/ We aimed to establish a rabbit model of vulnerable plaques (VPs) with the morphology and component characteristics of human VPs and to evaluate the microstructural features of VPs in vivo using intravascular optical coherence tomography (OCT). Twelve rabbits underwent endothelial denudation of the carotid artery and consumed a 1% high-cholesterol diet (HCD). They were equally divided into two groups: group A (modified needle injury) and group B (balloon injury). OCT was undertaken thrice before injury as well as 1 h and 12 weeks after injury. The degree of acute artery injury after endothelial denudation was detected by OCT. Twelve weeks after injury, OCT showed that both groups generated VPs which had thin fibrous caps and a large lipid core, whereas plaques in group A had smaller lipid arcs (). Histological findings demonstrated that a larger eccentricity index (EI) () and greater infiltration of macrophages () in group A than in group B. Qualitative and morphometric analyses of plaques showed a significant correlation between histological and OCT measurements. A combination of modified endothelial denudation and an HCD in rabbits produced more eccentric lesions similar to those seen in humans. These data suggest that OCT could be a useful tool for evaluation of the degree of injury and VPs in vivo. Yan Fang, Sining Hu, Jingbo Hou, Lingbo Meng, Shaosong Zhang, and Bo Yu Copyright © 2012 Yan Fang et al. All rights reserved. Role of Exogenous Nitric Oxide Donor in Treatment of Decompensated Hemorrhagic Shock in Normotensive and Hypertensive Rats Tue, 12 Jun 2012 15:24:49 +0000 http://www.hindawi.com/journals/bmri/2012/365195/ Introduction. In this study, we investigated the role of exogenous NO donor, sodium nitroprusside (SNP), on hemodynamic responses and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive rat. Methods. Male wistar rats were divided into normotensive and hypertensive groups (𝑛=12 each). Then, the animals were subjected to decompensated hemorrhagic shock by withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. After the shock period, the animals were randomly assigned to SNP-treated (0.5 mg/kg) and control groups (𝑛=6 each). MAP and heart rate (HR) were monitored throughout the experiment and 60 min after the administration of drug. Serum NO concentrations were measured. The survival rate was counted during next 72 h. Results. Infusion of SNP caused no significant changes in MAP and HR in normotensive and hypertensive animals. Hemorrhagic shock increased serum NO concentration and SNP administration reduced serum NO concentration in either normotensive or hypertensive groups. Survival counts during 72 h after experiment did not improve by SNP administration, and there were no significant differences between normotensive and hypertensive groups. Conclusion. SNP administration cannot improve hemodynamic responses and survival count during decompensated hemorrhagic shock in normotensive and hypertensive animals. Majid Khazaei and Babak Barmaki Copyright © 2012 Majid Khazaei and Babak Barmaki. All rights reserved. A Novel Model of Atherosclerosis in Rabbits Using Injury to Arterial Walls Induced by Ferric Chloride as Evaluated by Optical Coherence Tomography as well as Intravascular Ultrasound and Histology Mon, 14 May 2012 14:11:28 +0000 http://www.hindawi.com/journals/bmri/2012/121867/ This study aim was to develop a new model of atherosclerosis by FeCl3-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (𝑛=15) by combination of a cholesterol-rich diet and FeCl3-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (𝑛=3), 8 weeks (𝑛=6), and 12 weeks (𝑛=6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl3. The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time. Jinwei Tian, Sining Hu, Yanli Sun, Xiang Ban, Huai Yu, Nana Dong, Jian Wu, and Bo Yu Copyright © 2012 Jinwei Tian et al. All rights reserved. Transfer of Bone-Marrow-Derived Mesenchymal Stem Cells Influences Vascular Remodeling and Calcification after Balloon Injury in Hyperlipidemic Rats Mon, 14 May 2012 09:21:52 +0000 http://www.hindawi.com/journals/bmri/2012/165296/ Bone-marrow-derived mesenchymal stem cells (BM-MSCs) were found to markedly increase atherosclerotic lesion size. The aim of this paper was to investigate whether BM-MSCs contribute to vascular remodeling and calcification after balloon injury in hyperlipidemic rats. Labeled BM-MSCs were found in the lesion of hyperlipidemic rats after balloon injury. Comparing injury group, transferred BM-MSCs significantly triggered vascular negative remodeling, characterized by the changes of remodeling index (0.628±0.0293 versus 0.544±0.0217), neointimal area (0.078±0.015 mm2 versus 0.098±0.019 mm2), PCNA index (23.91±6.59% versus 43.11±5.31%), and percentage of stenosis (18.20±1.09% versus 30.58±1.21%). Apparent vascular calcification was detected in medial layers at 6 weeks after balloon angioplasty, which may be associated with upregulation of bone morphogenetic protein-2 (BMP-2). Our data indicated that unselected BM-MSCs transfer may induce vascular remodeling and calcification after balloon injury in hyperlipidemic rats. Jianquan Liao, Xiaochun Chen, Yongdong Li, Zhiping Ge, Hongyu Duan, Yunzeng Zou, and Junbo Ge Copyright © 2012 Jianquan Liao et al. All rights reserved. Temporal and Quantitative Analysis of Atherosclerotic Lesions in Diet-Induced Hypercholesterolemic Rabbits Wed, 14 Mar 2012 11:41:23 +0000 http://www.hindawi.com/journals/bmri/2012/506159/ The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs) and smooth muscle cells (SMCs) in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM). Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model. Qi Yu, Yafeng Li, Ahmed Bilal Waqar, Yanli Wang, Bingqiao Huang, Yulong Chen, Sihai Zhao, Peigang Yang, Jianglin Fan, and Enqi Liu Copyright © 2012 Qi Yu et al. All rights reserved. All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation Thu, 01 Mar 2012 09:28:17 +0000 http://www.hindawi.com/journals/bmri/2012/259693/ Background. All-trans-retinoic acid (atRA) is effective for many proliferative diseases. We investigated the protective effects of atRA against atherosclerosis. Methods. Rabbits were randomly allocated to receive basal diet or an HFD for 4 weeks. HFD group then received rosuvastatin (3 mg/day), atRA (5 mg/kg/day), or the same volume of vehicle, respectively, for next 8 weeks. Results. HFD group showed increases in plasma lipids and aortic plaque formation. P-selectin expression and fibrinogen binding on platelets or deposition on the intima of the aorta also increased significantly as did the levels of TNF-α, IL-6, and fibrinogen in plasma. After 8 weeks of treatment with atRA, there was a significant decrease in plasma lipids and improvement in aortic lesions. AtRA also inhibited the expression of P-selectin and fibrinogen binding on platelets and deposition on the intima of the aorta. Conclusion. AtRA can ameliorate HFD-induced AS in rabbits by inhibiting platelet activation and inflammation. Birong Zhou, Ying Pan, Zeping Hu, Xiaobian Wang, Jianxiong Han, Qing Zhou, Zhimin Zhai, and Yuan Wang Copyright © 2012 Birong Zhou et al. All rights reserved. The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis Thu, 22 Dec 2011 09:08:25 +0000 http://www.hindawi.com/journals/bmri/2012/464532/ Atherosclerosis is a chronic inflammatory disease that is mediated by both the innate and adaptive immune responses. T lymphocytes, that together with B cells are the cellular effectors of the adaptive immune system, are currently endowed with crucial roles in the development and progression of atherosclerosis. Costimulatory receptors are a class of molecules expressed by T lymphocytes that regulate the activation of T cells and the generation of effector T-cell responses. In this review we present the roles of costimulatory receptors of the tumour necrosis factor receptor (TNFR) superfamily in atherosclerosis and discuss the implications for future therapies that could be used to specifically modulate the immune response of pathogenic T cells in this disease. Ricardo F. Antunes, Juan Carlos Kaski, and Ingrid E. Dumitriu Copyright © 2012 Ricardo F. Antunes et al. All rights reserved. Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review Mon, 22 Mar 2010 10:22:51 +0000 http://www.hindawi.com/journals/bmri/2010/702836/ Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients. S. Umar, P. Steendijk, D. L. Ypey, D. E. Atsma, E. E. van der Wall, M. J. Schalij, and A. van der Laarse Copyright © 2010 S. Umar et al. All rights reserved. Glucagon Effects on Ischemic Vasodilatation in the Isolated Rat Heart Thu, 18 Mar 2010 16:08:12 +0000 http://www.hindawi.com/journals/bmri/2010/231832/ The myocardial reperfusion following ischemia leads to the ischemic vasodilation by affecting the release of various vasoactive substances, such as free radicals, NO, and histamine. In addition, some evidences suggest that glucagon itself may alter the release of those substances. In this study, we investigated the ischemic vasodilation of the isolated rat heart, as well as the concentrations of NO, TBARS, and histamine in the coronary venous effluent either in the presence or in the absence of glucagon. Our results showed that in the presence of glucagon, there was a faster restoration of coronary perfusion pressure during ischemic vasodilation compared to the absence of glucagon (124±5.6 versus 81±5.2 s) with no apparent changes in TBARS concentration. The glucagon's administration leads to the decreased release of histamine by approximately 35%. Biphasic release of NO in the presence of glucagon initially showed augmentation by 60%, followed by the significant attenuation of 45%. Mirko Rosic, Suzana Pantovic, Gvozden Rosic, Aleksandra Tomic-Lucic, Tatjana Labudovic, Vladimir Zivkovic, and Vladimir Jakovljevic Copyright © 2010 Mirko Rosic et al. All rights reserved. Characterization of Arterial Wave Reflection in Healthy Bonnet Macaques: Feasibility of Applanation Tonometry Tue, 10 Mar 2009 14:47:57 +0000 http://www.hindawi.com/journals/bmri/2009/876093/ Nonhuman primates are commonly used in cardiovascular research. Increased arterial stiffness is a marker of subclinical atherosclerosis and higher CV risk. We determined the augmentation index (AI) using applanation tonometry in 61 healthy monkeys (59% female, age 1–25 years). Technically adequate studies were obtained in all subjects and required 1.5±1.3 minutes. The brachial artery provided the highest yield (95%). AI was correlated with heart rate (HR) (𝑟=−0.65,𝑃<.001), crown rump length (CRL) (r = 0.42, P = .001), and left ventricular (LV) mass determined using echocardiography (𝑟=0.52,𝑃<.001). On multivariate analysis, HR (𝑃<.001) and CRL (P = .005) were independent predictors of AI (𝑅2=0.46,𝑃<.001). Body Mass Index (BMI) and AI were independent predictors of higher LV mass on multivariate analysis (𝑃<.001 and 𝑃=.03). In conclusion, applanation tonometry is feasible for determining AI. Reference values are provided for AI in bonnet macaques, in whom higher AI is related to HR and CRL, and in turn contributes to higher LV mass. Jason Lazar, Ghazanfar Qureshi, Haroon Kamran, Leonard A. Rosenblum, John G. Kral, and Louis Salciccioli Copyright © 2009 Jason Lazar et al. All rights reserved. Thermolabile Methylenetetrahydrofolate Reductase C677T Polymorphism and Homocysteine Are Risk Factors for Coronary Artery Disease in Moroccan Population Wed, 07 Mar 2007 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2007/080687/abs/ Increased plasma total homocysteine (tHcy) levels have been shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of CAD and plasma levels of tHcy. We also evaluated interactions between this polymorphism, mild elevated tHcy levels and conventional risk factors of CAD. Method. Using PCR-RFLP analysis, we studied the frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations in 400 subjects without and with CAD angiographically confirmed. There were 210 subjects with CAD and 190 subjects without CAD. Results. The frequencies of the C677T genotypes were 53% (59.5% in controls versus 48.1% in cases), 34.8% (32.1 in controls versus 37.1 in cases), and 11.8% (8.4% in controls versus 14.8% in cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were significantly different between case and control groups (P<.05). The 677T allele enhances the risk of CAD associated to HHcy (P<.01). In multivariate analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk factors. HHcy was only and independently influenced by MTHFR polymorphism and smoking habits, and it is a strong predictor of CAD independently of conventional risk factors. Conclusion. Our data suggest that HHcy is strongly and independently associated to CAD risk increase; and MTHFR C677T polymorphism and smoking habits were the main predictors of tHcy levels. The CAD risk increase is mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is mainly associated with the conventional risk factors. Nawal Bennouar, Abdellatif Allami, Houssine Azeddoug, Abdenbi Bendris, Abdelilah Laraqui, Amal El Jaffali, Nizar El Kadiri, Rachid Benzidia, Anwar Benomar, Seddik Fellat, and Mohamed Benomar Copyright © 2007 Nawal Bennouar et al. All rights reserved. Reduced Atherosclerotic Lesion Size in P-Selectin Deficient Apolipoprotein E-Knockout Mice Fed a Chow but Not a Fat Diet Tue, 04 Apr 2006 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2006/049193/abs/ Endothelial cells lining atherosclerotic, but not healthy sites, on human arteries express P-selectin. We investigated the role of P-selectin on the development of vascular lesions in an ApoE−/− male mice. Double-knockout (ApoE−/−, P-selectin-/-; DKO) were compared to single-knockout (ApoE−/−; SKO) mice. They were fed a chow or fat diet for 3, 6, 15, and 20 weeks, without any differences in cholesterol levels. DKO mice fed a chow diet exhibited a ratio of lesion area over media lower than SKO mice, for 3 (P<.03) , 6 (P<.001), and 15 (P<.02) weeks. DKO mice fed a fat diet showed a lower ratio only at 3 weeks. P-selectin deficiency in ApoE−/− mice has a protective effect in atherosclerotic lesions development. Reduction of lesion size depends on diet type and duration. A fat diet could neutralize the beneficial effects of P-selectin deficiency, inducing atherosclerotic lesions via probably other adhesion molecules. Marie-Claude Bourdillon, Jacques Randon, Lydie Barek, Kazem Zibara, Chantal Covacho, Robin N Poston, Elza Chignier, and John L. McGregor Copyright © 2006 Marie-Claude Bourdillon et al. All rights reserved. Identification, Structural, and Functional Characterization of a New Early Gene (6A3-5, 7 kb): Implication in the Proliferation and Differentiation of Smooth Muscle Cells Mon, 01 Jan 1900 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2005/797913/abs/ Arterial smooth muscle cells (SMCs) play a major role in atherosclerosis and restenosis. Differential display was used to compare transcription profiles of synthetic SMCs to proliferating rat cultured SMC line. An isolated cDNA band (6A3-5) was shown by northern (7 kb) to be upregulated in the proliferating cell line. A rat tissue northern showed differential expression of this gene in different tissues. Using 5′ RACE and screening of a rat brain library, part of the cDNA was cloned and sequenced (5.4 kb). Sequence searches showed important similarities with a new family of transcription factors, bearing ARID motifs. A polyclonal antibody was raised and showed a protein band of 175 kd, which is localized intracellularly. We also showed that 6A3-5 is upregulated in dedifferentiated SMC (P9) in comparison to contractile SMC ex vivo (P0). This work describes cloning, structural, and functional characterization of a new early gene involved in SMC phenotype modulation. Kazem Zibara, Gwenaële Garin, and John L. McGregor Copyright © 2005 Hindawi Publishing Corporation. All rights reserved.