Background —Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration impaired in hypercholesterolemia, we investigated whether plasma concentrations ADMA are elevated young, clinically asymptomatic hypercholesterolemic adults. We further studied such elevation levels was correlated with endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind,...

The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects atherosclerosis, reactivity measured forearm resistance vessels 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with 211 19 mg/dl, P less than 0.05). Each subject received intrabrachial artery infusions methacholine, which releases endothelium-derived relaxant factor, nitroprusside directly stimulates guanylate cyclase smooth muscle....

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose this study was to determine whether infusion L-arginine, precursor endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent hypercholesterolemic humans. Vascular reactivity measured forearm resistance vessels 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia 4.65...

It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating tone and structure. Recent developments gene transfer techniques have emerged as an exciting therapeutic option to treat disease. Several studies established feasibility direct vivo into vasculature by using reporter genes such beta-galactosidase or luciferase. To date no study has documented effects with cDNA encoding functional enzyme. This tests hypothesis endothelium-derived...

Background —Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose this study was examine relationship between plasma ADMA atherosclerosis humans. Methods Results —Subjects (n=116; age, 52±1 years; male:female ratio,...

The purpose of this study was to determine if chronic administration L-arginine, the precursor endothelium-derived relaxing factor (EDRF), normalizes endothelium-dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals. Male rabbits were fed (a) normal rabbit chow; (b) 1% cholesterol diet; or (c) diet supplemented by 2.25% L-arginine HCl drinking water. Arginine supplementation doubled plasma arginine levels without affecting serum values. After 10 wk, thoracic...

An endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), is elevated in patients with type 2 diabetes mellitus (DM). This study explored the mechanisms by which ADMA becomes DM.Male Sprague-Dawley rats were fed normal chow or high-fat diet (n=5 each) moderate streptozotocin injection to induce DM. Plasma was diabetic (1.33+/-0.31 versus 0.48+/-0.08 micromol/L; P<0.05). The activity, but not expression, dimethylaminohydrolase (DDAH) reduced and negatively...

Statins inhibit HMG-CoA reductase to reduce the synthesis of cholesterol and isoprenoids that modulate diverse cell functions. We investigated effect statins cerivastatin atorvastatin on angiogenesis in vitro vivo.Endothelial proliferation, migration, differentiation were enhanced at low concentrations (0.005 0.01 micromol/L) but significantly inhibited high statin (0.05 1 micromol/L). Antiangiogenic effects associated with decreased endothelial release vascular growth factor increased...

Background Hyperhomocysteinemia is a putative risk factor for cardiovascular disease, which also impairs endothelium-dependent vasodilatation. A number of other factors disease may exert their adverse vascular effects in part by elevating plasma levels asymmetric dimethylarginine (ADMA), an endogenous inhibitor nitric oxide synthase. Accordingly, we determined if homocysteine could increase ADMA levels. Methods and Results When endothelial or nonvascular cells were exposed to DL-homocysteine...

Background —Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Plasma levels ADMA are elevated in individuals with hypercholesterolemia or atherosclerosis. We postulated that reduced degradation may play a role the accumulation these individuals. Accordingly, we studied effects oxidized LDL (oxLDL) tumor necrosis factor-α (TNF-α) on by transformed human umbilical vein endothelial cells (ECV304) and enzyme dimethylaminohydrolase (DDAH), which...

Flow-mediated vasodilation is endothelium dependent. We hypothesized that flow activates a potassium channel on the endothelium, and activation of this leads to release endogenous nitrovasodilator, nitric oxide. To test hypothesis, rabbit iliac arteries were perfused at varying rates, constant pressure 60 mm Hg. Increments in induced proportional increases vessel diameter, which abolished by L,N-mono-methylarginine (the antagonist nitric-oxide synthesis). Barium chloride, depolarizing...

There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiological importance heart failure. A number studies have shown altered production by the endothelial constitutive isoform synthase (NOS), but there very little information on role inducible isoform.We analyzed NOS (iNOS) expression ventricular myocardium taken from 11 control subjects (who had died suddenly noncardiac causes), 10 donor hearts before implantation, and 51 patients with failure (24 dilated...

Experimental, epidemiologic and clinical studies have provided strong evidence that physical exercise has beneficial effects on multiple physiological variables affecting cardiovascular health (lipoprotein levels, rest blood pressure heart rate, carbohydrate tolerance, neurohormonal activity). Regular been shown to slow the progression of disease reduce morbidity mortality. More recently, exercise-induced increases in flow shear stress observed enhance vascular function structure. By...

Background and Aims Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore potential in the general population via data-mining approaches. Methods Using a novel approach for mining data pharmacovigilance, we queried over 16 million documents on 2.9 individuals examine...

Objective— Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we potential of endothelial cells (ECs) derived from human induced pluripotent (hiPSCs) to promote perfusion ischemic tissue in a murine model peripheral arterial disease. Methods Results— Endothelial differentiation was initiated by culturing hiPSCs 14 days media supplemented with BMP-4 growth factor. The hiPSC-ECs exhibited characteristics...

Background— Proton pump inhibitors (PPIs) are gastric acid–suppressing agents widely prescribed for the treatment of gastroesophageal reflux disease. Recently, several studies in patients with acute coronary syndrome have raised concern that use PPIs these may increase their risk major adverse cardiovascular events. The mechanism this possible effect is not known. Whether general population might also be at has been addressed. Methods and Results— Plasma asymmetrical dimethylarginine (ADMA)...