Biological functional relevance of asymmetric dimethylarginine (ADMA) in cardiovascular disease

Sara Franceschelli, Alessio Ferrone, Mirko Pesce, Graziano Riccioni, Lorenza Speranza, Sara Franceschelli, Alessio Ferrone, Mirko Pesce, Graziano Riccioni, Lorenza Speranza

Abstract

There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.

Figures

Figure 1.
Figure 1.
The role of DDAH1 in the metabolism of the nitric oxide synthase (NOS) antagonists asymmetric dimethylarginine (ADMA) and NG-monomethylarginine (NMMA). PRMTs, protein arginine methyltransferases; SDMA, symmetrical dimethylarginine.
Figure 2.
Figure 2.
Flow diagram outlining clinical conditions that have been reported to be associated with elevated ADMA concentration, and the interactive roles of ROS and ADMA in relating cardiovascular risk factors to pathophysiological changes in tissues that may underlie cardiovascular disease. ROS, reactive oxygen species; MMP, matrix metalloproteinase; VSMC, vascular smooth muscle cell.

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Source: PubMed

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