International Journal of Vascular Medicine

Erythromelalgia? A Clinical Study of People Who Experience Red, Hot, Painful Feet in the Community

D. Friberg, T. Chen, G. Tarr, and A. van Rij — Wed, 15 May 2013 19:20:14 +0000

We recruited a population of people who clinically suffer from the symptoms of erythromelalgia, red, hot, painful feet made worse by heat and improved by cooling, to better characterise this population and measure their quality of life (QOL). Ninety-two individuals completed the QOL surveys, and 56 individuals were clinically assessed. There was a 3 : 1 ratio of females to males with an average age of 61 years. The estimated prevalence of people who had clinical symptoms of erythromelalgia in the Dunedin community was 15/100,000. Only 27% of people had received a diagnosis for their symptoms despite seeking medical attention. People in the study population had worse quality of life than the general New Zealand population . In the majority of participants symptoms had a mild-moderate effect on their quality of life. The results of this study indicate that the number of people who have clinical symptoms of erythromelalgia is much greater than is commonly accepted and that the majority of these individuals go unrecognised by the medical profession despite seeking help. They have significantly diminished QOL with the majority of people having mild-to-moderate symptoms.

Association between Thrombophilia and the Post-Thrombotic Syndrome

Anat Rabinovich and Susan R. Kahn — Thu, 09 May 2013 14:45:42 +0000

The post thrombotic syndrome (PTS) is a chronic condition that develops in 20%–40% of deep vein thrombosis (DVT) patients. While risk factors that predispose to the development of venous thromboembolism (VTE) are widely known, factors that influence the development of PTS after DVT have not been well elucidated. Over 10% of the general population is affected by one or more identifiable inherited thrombophilias which have been shown to underlie at least 1/3 of cases of VTE. The various thrombophilias are important risk factors for VTE, but it is unknown whether they also increase the risk for development of PTS. We performed a review of studies that have reported on the association between thrombophilia and the development of PTS in populations of patients with DVT and with chronic venous ulcers. Studies vary with regards to the definition of PTS, study design, follow-up period, and present conflicting results. Based on these results, the question of whether thrombophilia predisposes to the development of PTS remains unanswered.

Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents

Sun, 31 Mar 2013 18:01:07 +0000

Coronary arteritis, a complication of Kawasaki disease (KD), can be refractory to immunoglobulin (IVIG) treatment. To determine the most effective alternative therapy, we compared the efficacy of different agents in a mouse model of KD. Vasculitis was induced by injection of Candida albicans water-soluble fractions (CAWS) into a DBA/2 mouse, followed by administration of IVIG, etanercept, methylprednisolone (MP), and cyclosporine-A (CsA). At 2 and 4 weeks, the mice were sacrificed, and plasma cytokines and chemokines were measured. CAWS injection induced active inflammation in the aortic root and coronary arteries. At 2 weeks, the vasculitis was reduced only by etanercept, and this effect persisted for the subsequent 2 weeks. At 4 weeks, IVIG and CsA also attenuated the inflammation, but the effect of etanercept was more significant. MP exerted no apparent effect at 2 or 4 weeks. The suppressive effect exerted by etanercept on cytokines, such as interleukin- (IL-)6, IL-12, IL-13, and tumor necrosis factor-α (TNF-α), was more evident than that of others. The extent of arteritis correlated with the plasma TNF-α levels, suggesting a pivotal role of TNF-α in KD. In conclusion, etanercept was most effective in suppressing CAWS-induced vasculitis and can be a new therapeutic intervention for KD.

Gene Expression of Adhesion Molecules in Endothelial Cells from Patients with Peripheral Arterial Disease Is Reduced after Surgical Revascularization and Pharmacological Treatment

Wed, 27 Feb 2013 11:42:33 +0000

Atherosclerosis is an inflammatory disease characterized by immunological activity, in which endothelial dysfunction represents an early event leading to subsequent inflammatory vascular damage. We investigated gene expression of the adhesion molecules (AMs) ICAM-1, VCAM-1, and 1-integrin in endothelial cells (ECs) isolated from venous blood (circulating EC, cEC) and purified from femoral plaques (pEC) obtained from 9 patients with peripheral artery disease (PAD) submitted to femoral artery thrombendarterectomy (FEA). In addition, in peripheral blood mononuclear cells (PBMCs) of the same subjects, we investigated gene expression of IFN-, IL-4, TGF-, and IL-10. Patients were longitudinally evaluated 1 month before surgery, when statin treatment was established, at the time of surgery, and after 2 and 5 months. All AM mRNA levels, measured by means of real-time PCR, in cEC diminished during the study, up to 41–50% of initial levels at followup. AM mRNA expression was significantly higher in pEC than in cEC. During the study, in PBMCs, TGF- and IL-10 mRNA levels remained unchanged while IFN- and IL-4 levels increased; however, the ratio IFN-/IL-4 showed no significant modification. In PAD patients, FEA and statin treatment induce a profound reduction of AM expression in cEC and affect cytokine mRNA expression in PBMCs.

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

Marcelo Cury, Fernanda Zeidan, and Armando C. Lobato — Mon, 14 Jan 2013 14:22:53 +0000

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

Inflammation and Vascular Remodeling

Tue, 13 Nov 2012 15:09:41 +0000

Blood Flow Restricted Exercise and Vascular Function

Masahiro Horiuchi and Koichi Okita — Mon, 22 Oct 2012 15:43:57 +0000

It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR) leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

ABO Blood Groups and Cardiovascular Diseases

Hanrui Zhang, Ciarán J. Mooney, and Muredach P. Reilly — Mon, 22 Oct 2012 11:58:55 +0000

ABO blood groups have been associated with various disease phenotypes, particularly cardiovascular diseases. Cardiovascular diseases are the most common causes of death in developed countries and their prevalence rate is rapidly growing in developing countries. There have been substantial historical associations between non-O blood group status and an increase in some cardiovascular disorders. Recent GWASs have identified ABO as a locus for thrombosis, myocardial infarction, and multiple cardiovascular risk biomarkers, refocusing attention on mechanisms and potential for clinical advances. As we highlight in this paper, more recent work is beginning to probe the molecular basis of the disease associations observed in these observational studies. Advances in our understanding of the physiologic importance of various endothelial and platelet-derived circulating glycoproteins are elucidating the mechanisms through which the ABO blood group may determine overall cardiovascular disease risk. The role of blood group antigens in the pathogenesis of various cardiovascular disorders remains a fascinating subject with potential to lead to novel therapeutics and prognostics and to reduce the global burden of cardiovascular diseases.

The Influence of Endothelial Function and Myocardial Ischemia on Peak Oxygen Consumption in Patients with Coronary Artery Disease

Thu, 11 Oct 2012 19:11:59 +0000

Impaired endothelial function has been shown to limit exercise in coronary artery disease (CAD) patients and has been implicated in myocardial ischemia. However, the association of endothelial function and ischemia on peak exercise oxygen consumption (VO2) has not been previously reported. A total of 116 CAD patients underwent standard exercise stress testing, during which VO2 was measured. On a separate day, endothelial-dependent and -independent function were assessed by ultrasound using flow-mediated arterial vasodilation (FMD) and sublingual glyceryl trinitrate administration (GTNMD) of the brachial artery. Patients with exercise-induced myocardial ischemia had lower FMD than nonischemic patients ( versus , ), but there was no difference in GTNMD ( versus , ). Analyses revealed that both FMD () and GTNMD () were related to peak VO2. However, neither the presence of ischemia () nor the interaction of ischemia with FMD () and GTNMD () was related to peak VO2. These data suggest that poor endothelial function, potentially via impaired NO production and smooth muscle dysfunction, may be an important determinant of exercise capacity in patients with CAD, independent of myocardial ischemia.

Benfotiamine Counteracts Smoking-Induced Vascular Dysfunction in Healthy Smokers

Wed, 03 Oct 2012 19:28:54 +0000

Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% (∗∗ versus baseline) an effect significantly reduced by benfotiamine treatment to 25%∗§ (∗ versus baseline, § versus smoking alone). Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

MicroRNAs in Vascular Biology

Munekazu Yamakuchi — Wed, 26 Sep 2012 11:56:04 +0000

Vascular inflammation is an important component of the pathophysiology of cardiovascular diseases, such as hypertension, atherosclerosis, and aneurysms. All vascular cells, including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and infiltrating cells, such as macrophages, orchestrate a series of pathological events. Despite dramatic improvements in the treatment of atherosclerosis, the molecular basis of vascular inflammation is not well understood. In the last decade, microRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Each miRNAs suppresses a set of genes, forming complex regulatory network. This paper provides an overview of current advances that have been made in revealing the roles of miRNAs during vascular inflammation. Recent studies show that miRNAs not only exist inside cells but also circulate in blood. These circulating miRNAs are useful biomarkers for diagnosis of cardiovascular diseases. Furthermore, recent studies demonstrate that circulating miRNAs are delivered into certain recipient cells and act as messengers. These studies suggest that miRNAs provide new therapeutic opportunities.

The Effects of Walking or Walking-with-Poles Training on Tissue Oxygenation in Patients with Peripheral Arterial Disease

Tue, 25 Sep 2012 16:22:44 +0000

This randomized trial proposed to determine if there were differences in calf muscle StO2 parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program. Data were collected on 85 patients who were randomized to a traditional walking program () or walking-with-poles program () of exercise training. Patients walked for 3 times weekly for 12 weeks. Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests ( traditional walking and walking-with-poles). Using the near-infrared spectroscopy measures, StO2 was measured prior to, during, and after exercise. At baseline, calf muscle oxygenation decreased from % prior to the treadmill test to % at peak exercise. The time elapsed prior to reaching nadir StO2 values increased more in the traditional walking group when compared to the walking-with-poles group. Likewise, absolute walking time increased more in the traditional walking group than in the walking-with-poles group. Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program. In conclusion, the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD.

Effects of the Intensity of Leg Isometric Training on the Vasculature of Trained and Untrained Limbs and Resting Blood Pressure in Middle-Aged Men

Anthony W. Baross, Jonathan D. Wiles, and Ian L. Swaine — Sun, 09 Sep 2012 15:42:40 +0000

The purpose of this study was to establish whether changes in resting blood pressure and the vasculature of trained and untrained limbs are dependent on training intensity, following isometric-leg training. Thirty middle-aged males undertook an 8 week training programme (4×2 min bilateral-leg isometric contractions 3 times per week). Two groups trained at either high (HI; 14%MVC) or low (LO; 8%MVC) intensity a third group (CON) acted as controls. All parameters were measured at baseline, 4-weeks and post-training. Resting SBP (−10.8±7.9 mmHg), MAP (−4.7±6.8 mmHg) and HR (−4.8±5.9 b·min−1) fell significantly in the HI group post-training with concomitant significant increases in resting femoral mean artery diameter (FMAD; 1.0±0.4 mm), femoral mean blood velocity (FMBV; 0.68±0.83 cm·s−1), resting femoral artery blood flow (FABF; 82.06±31.92 ml·min−1) and resting femoral vascular conductance (FVC, 45%). No significant changes occurred in any brachial artery measure nor in any parameters measured in the LO or CON groups. These findings show that training-induced reductions in resting blood pressure after isometric-leg training in healthy middle-aged men are associated with concomitant adaptations in the local vasculature, that appear to be dependent on training intensity and take place in the later stages of training.

Common Carotid Artery Diameter and Cardiovascular Risk Factors in Overweight or Obese Postmenopausal Women

Tue, 21 Aug 2012 13:44:22 +0000

Arterial diameter is an underutilized indicator of vascular health. We hypothesized that interadventitial and lumen diameter of the common carotid artery would be better indicators of vascular health than carotid plaque or intima media thickness (IMT). Participants were 491 overweight or obese, postmenopausal women who were former or current hormone therapy (HT) users, 52–62 years, with waist circumference >80cm. We evaluated cross-sectional associations of cardiovascular risk factors with carotid measures, by HT status. Former HT users had a worse cardiovascular profile than current HT users: larger adventitial (6.94 mm versus 6.79 mm) and lumen diameter (5.44 mm versus 5.31 mm, both 𝑃<0.01) independent of cardiovascular risk factors; IMT and plaque were similar. Larger diameters were best explained by former HT use, higher pulse pressure, and greater weight. Independent of potential confounders, overweight and obese postmenopausal former HT users had larger carotid diameters than current HT users. Carotid diameter should be considered in studies of HT.

Recent Advances in Pharmacotherapy Development for Abdominal Aortic Aneurysm

Koichi Yoshimura and Hiroki Aoki — Tue, 21 Aug 2012 10:43:00 +0000

Abdominal aortic aneurysm (AAA) is a common disease causing segmental expansion and rupture of the aorta with a high mortality rate. The lack of nonsurgical treatment represents a large and unmet need in terms of pharmacotherapy. Advances in AAA research revealed that activation of inflammatory signaling pathways through proinflammatory mediators shifts the balance of extracellular matrix (ECM) metabolism toward tissue degradation. This idea is supported by experimental evidence in animal models that pharmacologic intervention at each pathological step can prevent AAA development. Previously, we identified c-Jun N-terminal kinase (JNK), a pro-inflammatory signaling molecule, as a therapeutic target for AAA. Abnormal activation of JNK in AAA tissue regulates multiple pathological processes in a coordinated manner. Pharmacologic inhibition of JNK tips the ECM balance back towards repair rather than degradation. Interventions targeting signaling molecules such as JNK in order to manipulate multiple pathological processes may be an ideal therapeutic strategy for AAA. Furthermore, the development of biomarkers as well as appropriate drug delivery systems is essential to produce clinically practical pharmacotherapy for AAA.

Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment

Tue, 07 Aug 2012 09:10:17 +0000

Carotid-to-radial pulse wave velocity (PWVcr) has been proposed to evaluate endothelial function. However, the measurement of PWVcr is not without limitations. A new simple approach could have wide application. Stiffness index (SI) is obtained by analysis of the peripheral pulse wave and gives reproducible information about stiffness of large arteries. This study assessed the effects of hyperemia on SI and compared it with PWVcr in 14 healthy subjects. Both were measured at rest and during 8 minutes after ischemia. SI temporal course was determined. At 1 minute, SI and PWVcr decreased (5.58±0.24 to 5.34±0.23 m/s, 𝑃<0.05; 7.8±1.0 to 7.2±0.9 m/s; 𝑃<0.05, resp.). SI was positively related to PWVcr in baseline (𝑟=0.62 , 𝑃<0.05), at 1 minute (𝑟=0.79, 𝑃<0.05), and during the whole experimental session (𝑟=0.52, 𝑃<0.05). Conclusion. Hyperemia significantly decreases SI in healthy subjects. SI was related to PWVcr and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness.

Further Clinical Validation of the Walking Impairment Questionnaire for Classification of Walking Performance in Patients with Peripheral Artery Disease

S. P. Sagar, P. M. Brown, D. T. Zelt, W. L. Pickett, and J. E. Tranmer — Thu, 02 Aug 2012 11:24:44 +0000

The purpose of this study was to further validate the Walking Impairment Questionnaire (WIQ) as a self-report tool to aid in the clinical identification of walking ability of patients with peripheral artery disease (PAD). 132 patients with PAD and an ankle brachial index (ABI) ≤0.90 were enrolled; 123 provided complete data for the WIQ and standardized graded treadmill test. The WIQ scores were consistent with reported scores in other studies. The absolute claudication distance (ACD) ranged from 42.3 to 1589.2 meters; the peak walking time (PWT) ranged from 68 to 1800 seconds. Adjusted WIQ scores were positively and moderately associated with the log transformed ACD and PWT (r>.53, P<.001). Based on the area under the curve analysis, an overall WIQ score of 42.5 or less identified low performers (sensitivity 0.90, specificity 0.73); the combined subscale score of distance and stair of 75.5 or more identified high performers (sensitivity 0.41, specificity 0.90). We conclude that WIQ cut-offs appropriately classify walking performance in PAD patients, making this a potentially useful clinical tool. Consideration needs to be given to incorporating a standardized WIQ version into practice guidelines and the use of innovative strategies to facilitate clinical uptake.

Role of Peroxisome Proliferator-Activated Receptor-γ in Vascular Inflammation

Kousei Ohshima, Masaki Mogi, and Masatsugu Horiuchi — Tue, 24 Jul 2012 08:16:10 +0000

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ is a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γ activation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γ ligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γ activation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γ involvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.

Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling

Tue, 17 Jul 2012 14:54:40 +0000

Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 μg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production.

Anti-Inflammatory Effects of Epoxyeicosatrienoic Acids

Scott J. Thomson, Ara Askari, and David Bishop-Bailey — Mon, 16 Jul 2012 11:14:21 +0000

Epoxyeicosatrienoic acids (EETs) are generated by the activity of both selective and also more general cytochrome p450 (CYP) enzymes on arachidonic acid and inactivated largely by soluble epoxide hydrolase (sEH), which converts them to their corresponding dihydroxyeicosatrienoic acids (DHETs). EETs have been shown to have a diverse range of effects on the vasculature including relaxation of vascular tone, cellular proliferation, and angiogenesis as well as the migration of smooth muscle cells. This paper will highlight the growing evidence that EETs also mediate a number of anti-inflammatory effects in the cardiovascular system. In particular, numerous studies have demonstrated that potentiation of EET activity using different methods can inhibit inflammatory gene expression and signalling pathways in endothelial cells and monocytes and in models of cardiovascular diseases. The mechanisms by which EETs mediate their effects are largely unknown but may include direct binding to peroxisome proliferator-activated receptors (PPARs), G-protein coupled receptors (GPCRs), or transient receptor potential (TRP) channels, which initiate anti-inflammatory signalling cascades.

A Model of Left Ventricular Dysfunction Complicated by CAWS Arteritis in DBA/2 Mice

Sun, 08 Jul 2012 08:18:09 +0000

It was reported previously that a Candida albicans water-soluble fraction (CAWS), including a mannoprotein and β-glucan complex, has strong potency in inducing fatal necrotizing arteritis in DBA/2 mice. In this study, histopathological changes and cardiac function were investigated in this system. One mg/day of CAWS was given to DBA/2 mice via peritoneal injection for five days. The CAWS-treated DBA/2 mice were induced aortitis and died at an incidence of 100% within several weeks. Histological findings included stenosis in the left ventricular outflow tract (LVOT) and severe inflammatory changes of the aortic valve with fibrinoid necrosis. Cardiomegaly was observed and heart weight increased 1.62 fold (𝑃<0.01). Echocardiography revealed a severe reduction in contractility and dilatation of the cavity in the left ventricle (LV): LV fractional shortening (LVFS) decreased from 71% to 38% (𝑃<0.01), and the LV end-diastolic diameter (LVDd) increased from 2.21 mm to 3.26 mm (𝑃<0.01). The titer of BNP mRNA increased in the CAWS-treated group. Severe inflammatory changes resulting from CAWS brought about lethal LV dysfunction by aortic valve deformation with LVOT stenosis. This system is proposed as an easy and useful experimental model of heart failure because CAWS arteritis can be induced by CAWS injection alone.

Expression and Function of Ephrin-B1 and Its Cognate Receptor EphB2 in Human Abdominal Aortic Aneurysm

Thu, 05 Jul 2012 09:49:49 +0000

We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5±2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410±0.046 versus 1.198±0.252, 𝑃=0.027) and EphB2 (0.764±0.212 versus 1.272±0.137, 𝑃=0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7±12.7% (𝑃=0.01) and 50.7±13.1% (𝑃=0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought.

Effects of Statins on Cardiorenal Syndrome

Tue, 26 Jun 2012 13:38:15 +0000

Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.

Involvement of Inflammation and Adverse Vascular Remodelling in the Blood Pressure Raising Effect of Repeatedly Heated Palm Oil in Rats

Thu, 21 Jun 2012 11:06:44 +0000

Oil thermoxidation during deep frying generates harmful oxidative free radicals that induce inflammation and increase the risk of hypertension. This study aimed to investigate the effect of repeatedly heated palm oil on blood pressure, aortic morphometry, and vascular cell adhesion molecule-1 (VCAM-1) expression in rats. Male Sprague-Dawley rats were divided into five groups: control, fresh palm oil (FPO), one-time-heated palm oil (1HPO), five-time-heated palm oil (5HPO), or ten-time-heated palm oil (10HPO). Feeding duration was six months. Blood pressure was measured at baseline and monthly using tail-cuff method. After six months, the rats were sacrificed and the aortic arches were dissected for morphometric and immunohistochemical analyses. FPO group showed significantly lower blood pressure than all other groups. Blood pressure was increased significantly in 5HPO and 10HPO groups. The aortae of 5HPO and 10HPO groups showed significantly increased thickness and area of intima-media, circumferential wall tension, and VCAM-1 than other groups. Elastic lamellae were disorganised and fragmented in 5HPO- and 10HPO-treated rats. VCAM-1 expression showed a significant positive correlation with blood pressure. In conclusion, prolonged consumption of repeatedly heated palm oil causes blood pressure elevation, adverse remodelling, and increased VCAM-1, which suggests a possible involvement of inflammation.

Carotid Velocities Determine Cerebral Blood Flow Deficits in Elderly Men with Carotid Stenosis <50%

Arkadiusz Siennicki-Lantz, Per Wollmer, and Sölve Elmståhl — Tue, 19 Jun 2012 14:26:40 +0000

To examine if mild carotid stenosis correlates with silent vascular brain changes, we studied a prospective population-based cohort “Men born in 1914.” Data from followups at ages 68 and 81, have been used. Carotid ultrasound was performed at age 81, and cerebral blood flow (CBF) was measured with SPECT at age 82. Out of 123 stroke-free patients, carotid stenosis <50% was observed in 94% in the right and 89% in the left internal carotid arteries (ICAs). In these subjects, Peak Systolic Velocities in ICA correlated negatively with CBF in a majority of several brain areas, especially in mesial temporal area. Results were limited to normotensive until their seventies, who developed late-onset hypertension with a subsequent blood pressure, pulse pressure, and ankle-brachial index growth. Elderly with asymptomatic carotid stenosis <50% and peak systolic velocities in ICA 0.7–1.3 m/s, should be offered an intensified pharmacotherapy to prevent stroke or silent cerebrovascular events.

Imaging-Based Biomarkers: Characterization of Post-Kawasaki Vasculitis in Infants and Hypertension Phenotype in Rat Model

Roch Listz Maurice, Nagib Dahdah, and Johanne Tremblay — Thu, 14 Jun 2012 13:11:19 +0000

Background. Investigating the mechanical properties of the arteries is essential in cardiovascular diseases. Recent imaging modalities allow mapping mechanical properties within the arterial wall. Aims. We report the potential of imaging-based biomarker (ImBioMark) to investigate the effect of aging on the rat. We also present preliminary data with ImBioMark characterizing vascular sequelae of Kawasaki disease (KD) in young humans. Methods. We investigated in vivo the effect of aging on male Brown Norway (BN) rats’ (𝑛=5) carotid stiffness. In a second experiment, the impact of KD on the ascending aorta (AA) was examined in KD children (𝑛=2) aged 13 ± 1.41 years old compared to KD-free children (𝑛=5) aged 13.13 ± 0.18 years old. Results. The stiffness of BN’s carotid artery was three times stiffer in the old rats, with a turning point at 40 weeks old (𝑃=0.001). KD had a very significant impact on the AA stiffness with strain estimates of 2.39 ± 0.51% versus 4.24 ± 0.65% in controls (𝑃<0.001). Conclusion. ImBioMark phenotypes hypertension in rat models noninvasively in vivo without resorting to euthanasia. Quantifying aortic wall remodeling is also feasible in humans. Future investigations target human cardiovascular disease.

Selective Gene Expression Analysis of Muscular and Vascular Components in Hearts Using Laser Microdissection Method

Tue, 12 Jun 2012 14:10:39 +0000

Background. The heart consists of various kinds of cell components. However, it has not been feasible to separately analyze the gene expression of individual components. The laser microdissection (LMD) method, a new technology to collect target cells from the microscopic regions, has been used for malignancies. We sought to establish a method to selectively collect the muscular and vascular regions from the heart sections and to compare the marker gene expressions with this method. Methods and Results. Frozen left ventricle sections were obtained from Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHR-SP) at 24 weeks of age. Using the LMD method, the muscular and vascular regions were selectively collected under microscopic guidance. Real-time RT-PCR analysis showed that brain-type natriuretic peptide (BNP), a marker of cardiac myocytes, was expressed in the muscular samples, but not in the vascular samples, whereas α-smooth muscle actin, a marker of smooth muscle cells, was detected only in the vascular samples. Moreover, SHR-SP had significantly greater BNP upregulation than WKY (𝑃<0.05) in the muscular samples. Conclusions. The LMD method enabled us to separately collect the muscular and vascular samples from myocardial sections and to selectively evaluate mRNA expressions of the individual tissue component.

Correlations between Endothelial Functions and ROS Detection in Diabetic Microvascular Wall: Early and Late Ascorbic Acid Supplementation

Pattarin Sridulyakul, Natchaya Wongeak-in, and Suthiluk Patumraj — Mon, 28 May 2012 10:39:56 +0000

The correlation between endothelial function and reactive oxygen species detecting from diabetic microvascular wall and the antioxidant effect of ascorbic acid (AA) during early and late phases of diabetic induction were determined. Male Spraque-Dawley rats were divided into four groups: control, diabetes rats (DM, using iv.injection of 55 mg/kg BW streptozotocin, (STZ)), and two groups of DM rats treated with AA (1 g/L, (STZ)) starting on day 2 (DM + AAday2) and week 6th (DM + AA6wk). On 12th week after STZ injection, the findings showed that in DM group, Ach (10−5 M)-induced vasodilatation was decreased, while the number of leukocyte adhesion was increased significantly (𝑃<0.01). Interestingly, these abnormalities induced by DM could be protected or improved in both AA-treated groups, DM + AAday2 and DM + AA6wk. By using dihydrorhodamine 123, our findings also indicated that the existing of ROS productions on diabetic arteriolar and venular walls were different significantly (ROSarteriole = 165.89 ± 24.59 and ROSvenule = 172.26 ± 34.70) (𝑃<0.05). Moreover by using BH4 inhibitor to induce increase in arteriolar ROS, the results also confirmed that AA could improve endothelial function with closed correlation to its potential to reduce vascular ROS content.

Assessments of Arterial Stiffness and Endothelial Function Using Pulse Wave Analysis

Lee Stoner, Joanna M. Young, and Simon Fryer — Mon, 14 May 2012 10:26:19 +0000

Conventionally, the assessments of endothelial function and arterial stiffness require different sets of equipment, making the inclusion of both tests impractical for clinical and epidemiological studies. Pulse wave analysis (PWA) provides useful information regarding the mechanical properties of the arterial tree and can also be used to assess endothelial function. PWA is a simple, valid, reliable, and inexpensive technique, offering great clinical and epidemiological potential. The current paper will outline how to measure arterial stiffness and endothelial function using this technique and include discussion of validity and reliability.

Correlation between US-PSV and 64-Row MDCTA with Advanced Vessel Analysis in the Quantification of 50–70% Carotid Artery Stenosis

Sun, 22 Apr 2012 14:48:29 +0000

Purpose. To correlate ultrasonographic peak systolic velocity (US-PSV) and 64-row multidetector computed tomography angiography (MDCTA) with advanced vessel analysis (AVA) software in the quantification of 50–70% carotid artery stenosis. Materials and methods. 199 consecutive patients (247 arteries) with internal carotid artery (ICA) or third proximal bifurcation stenosis. Each patient was studied by duplex US (DUS) and 64-row MDCTA with AVA software. Results. DUS showed PSV measurements less than 125 cm/s in 51 carotid stenosis and a value greater than this in 196 arteries. 64-row MDCTA AVA software showed a grade of stenosis less than 50% in 42 carotid arteries while a greater 70% was found in 4 carotid arteries; then, carotid arteries with stenosis percentage between 50% and 70% were 201. Linear regression analysis showed a good linear correlation (𝑟=0.88) between MDCTA-AVA software percentage stenosis and PSV: between 50% grade of stenosis and PSV value corresponding to 133,6 cm/sec and between 70% stenosis and PSV value corresponding to 268 cm/sec. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) of this analysis were 93%, 82%, 97%, 75%, respectively. Conclusion. Linear correlation between PSV data and grade of stenosis from 50% to 70% obtained with 64-row MDCTA AVA software. Main PSV value corresponding to 50% and 70% grade of stenosis at AVA analysis.