Recent advances in understanding endothelial dysfunction in atherosclerosis.
Over the last two decades, it has become evident that decreased bioavailability of endothelial nitric oxide (NO) produced from endothelial NO synthase (eNOS), referred to as endothelial dysfunction, plays a crucial role in the development and progression of atherosclerosis. Much progress has been made in understanding the mechanisms of decreased endothelial NO bioavailability at the levels of regulation of eNOS gene expression, eNOS enzymatic activity and NO inactivation. Initial studies suggest that increasing eNOS gene expression would improve endothelial NO release in the hope of inhibiting the progression of atherosclerosis. Recent experimental studies, however, do not always support this therapeutic concept and show some evidence that overexpression of eNOS in atherosclerosis may be even harmful for the disease progression.Thus, recent research to improve endothelial function in atherosclerosis has focused on regulation of eNOS enzymatic activity and prevention of NO inactivation by oxidative stress. Since the role of oxidative stress in endothelial NO bioavailability has been reviewed in a large number of comprehensive articles, this article focuses on the relevant regulatory mechanisms of eNOS enzymatic activity that are emerging to play a role in endothelial dysfunction in atherosclerosis.
Yang
Zhihong
Z
Vascular Biology Laboratory, Department of Medicine, Division of Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland. zhihong.yang@unifr.ch
Ming
Xiu-Fen
XF
D000818:Animals; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III