Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: implications for atherogenesis

Atherosclerotic coronary heart disease is the leading cause of morbidity and mortality in industrialized countries, and endothelial dysfunction is considered a precursor phenomenon. The nitric oxide produced by the endothelium under the action of endothelial nitric oxide synthase has important antiatherogenic functions. Its reduced bioavailabilty is the beginning of the atherosclerotic process. The addition of two methyl radicals to arginine, through the action of methyltransferase nuclear proteins, produces asymmetric dimethylarginine, which competes with L-arginine and promotes a reduction in nitric oxide formation in the vascular wall. The asymmetric dimethylarginine, which is itself considered a mediator of the vascular effects of the several risk factors for atherosclerosis, can be eliminated by renal excretion or by the enzymatic action of the dimethylarginine dimethylaminohydrolases. Several basic science and clinical research studies suggest that the increase in asymmetric dimethylarginine occurs in the context of chronic renal insufficiency, dyslipidemia, high blood pressure, diabetes mellitus, and hyperhomocysteinemy, as well as with other conditions. Therapeutic measures to combat atherosclerosis may reverse these asymmetric dimethylarginine effects or at least reduce the concentration of this chemical in the blood. Such an effect can be achieved with competitor molecules or by increasing the expression or activity of its degradation enzyme. Studies are in development to establish the true role of asymmetric dimethylarginine as a marker and mediator of atherosclerosis, with possible therapeutic applications. The main aspects of the formation and degradation of asymmetric dimethylarginine and its implication in the atherogenic process will be addressed in this article.

Bibliographic Details

Main Authors:	Landim,Maurício Batista Paes, Casella Filho,Antônio, Chagas,Antônio Carlos Palandri
Format:	Digital revista
Language:	English
Published:	Faculdade de Medicina / USP 2009
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322009000500015
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