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Publication : Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators?

First Author  Caplin B Year  2012
Journal  Arterioscler Thromb Vasc Biol Volume  32
Issue  6 Pages  1343-53
PubMed ID  22460557 Mgi Jnum  J:196921
Mgi Id  MGI:5490198 Doi  10.1161/ATVBAHA.112.247726
Citation  Caplin B, et al. (2012) Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators?. Arterioscler Thromb Vasc Biol 32(6):1343-53
abstractText  The asymmetric methylarginines inhibit nitric oxide synthesis in vivo by competing with L-arginine at the active site of nitric oxide synthase. High circulating levels of asymmetric dimethylarginine predict adverse outcomes, specifically vascular events but there is now increasing experimental and epidemiological evidence that these molecules, and the enzymes that regulate this pathway, play a mechanistic role in cardiovascular diseases. Recent data have provided insight into the impact of altered levels of these amino acids in both humans and rodents, however these reports also suggest a simplistic approach based on measuring, and modulating circulating asymmetric dimethylarginine alone is inadequate. This review outlines the basic biochemistry and physiology of endogenous methylarginines, examines both the experimental and observational evidence for a role in disease pathogenesis, and examines the potential for therapeutic regulation of these molecules.
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