Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction is a hallmark of cardiovascular disease, and the l-arginine:NO pathway plays a critical role in determining endothelial function. Recent studies suggest that smoking, a well-recognized risk factor for vascular disease, may interfere with l-arginine and NO metabolism; however, this remains poorly characterized. Accordingly, we performed a series of complementary in vivo and in vitro studies to elucidate the mechanism by which cigarette smoke adversely affects endothelial function. In current smokers, plasma levels of asymmetrical dimethyl-arginine (ADMA) were 80% higher (P = 0.01) than nonsmokers, whereas citrulline (17%; P < 0.05) and N-hydroxy-l-arginine (34%; P < 0.05) were significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly affected endothelial arginine metabolism with reductions in the intracellular content of citrulline (81%), N-hydroxy-l-arginine (57%), and arginine (23%), while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake in conjunction with a 34% reduction in expression of the arginine transporter, CAT1. In conjunction with these studies, CSE significantly reduced the activity of eNOS and NO production by endothelial cells, while stimulating the production of reactive oxygen species. In conclusion, cigarette smoke adversely affects the endothelial l-arginine NO synthase pathway, resulting in reducing NO production and elevated oxidative stress. In conjunction, exposure to cigarette smoke increases ADMA concentration, the latter being a risk factor for cardiovascular disease.
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PMID:Adverse effects of cigarette smoke on NO bioavailability: role of arginine metabolism and oxidative stress. 1692 96

Atrial fibrillation (AF) may cause thrombus formation in the left atrial appendage (LAA). Thrombus formation is associated with LAA endocardial dysfunction. Because asymmetrical dimethylarginine (ADMA) can cause endothelial dysfunction by decreasing nitric oxide (NO) formation, we investigated plasma ADMA and nitrite/nitrate (NO(X)) levels and myocardial dimethylarginine dimethylaminohydrolase-2 (DDAH-2), protein arginine methyltransferase-1 (PRMT-1), and endothelial NO synthase (eNOS) protein contents from AF dogs. The results displayed that plasma ADMA level significantly increased, and plasma NO(X) concentration significantly decreased. Compared with normal heart, DDAH-2 expression was unchanged in the fibrillating atria. However, the DDAH activity was significantly decreased in the fibrillating atria. PRMT-1 expression significantly increased in the LAA and in the left atrium (LA). ENOS expression significantly decreased in the LA. ENOS and PRMT-1 expressions were unchanged in the right atria. Our results suggested that the DDAH-PRMT-ADMA system maybe play a pivotal role in regulating endothelial function in AF.
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PMID:Variance of DDAH/PRMT/ADMA pathway in atrial fibrillation dogs. 1895 71

The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function.
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PMID:High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function. 2722 80