Implication of eNOS Uncoupling in Cardiovascular Disease

Abstract

Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) represents a key vasoprotective factor. Under conditions of cardiovascular diseases, such as hypertension, diabetes, and atherosclerosis, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential cofactor for the eNOS enzyme, and deficiency of l-arginine, the eNOS substrate, and/or eNOS S-glutathionylation. Reversal of eNOS uncoupling may represent a novel therapeutic strategy for the prevention and treatment of cardiovascular diseases.