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.