Nitric oxide, NAD(P)H oxidase, and atherosclerosis.
The endothelial cell layer plays a major role in the development and progression of atherosclerosis. Endothelial NO synthase (eNOS) produces nitric oxide (NO) from L-arginine. NO can rapidly react with reactive oxygen species to form peroxynitrite. This reduces NO availability, impairs vasodilatation, and mediates proinflammatory and prothrombotic processes such as leukocyte adhesion and platelet aggregation. In the vessel wall, specific NAD(P)H oxidase complexes are major sources of reactive oxygen species. These NAD(P)H oxidases can transfer electrons across membranes to oxygen and generate superoxide anions. The short-lived superoxide anion rapidly dismutates to hydrogen peroxide, which can further increase the production of reactive oxygen species. This can lead to uncoupling of eNOS switching enzymatic activity from NO to superoxide production. This review describes the structure and regulation of different NAD(P)H oxidase complexes. We will also focus on NO/superoxide anion balance as modulated by hemodynamic forces, vasoconstrictors, and oxidized low-density lipoprotein. We will then summarize the recent advances defining the role of nitric oxide and NAD(P)H oxidase-derived reactive oxygen species in the development and progression of atherosclerosis. In conclusion, novel mechanisms affecting the vascular NO/superoxide anion balance will allow the development of therapeutic strategies in the treatment of cardiovascular diseases.
Muller
Gregor
G
Department of Vascular Endothelium and Microcirculation, University of Technology Dresden, Dresden, Germany.
Morawietz
Henning
H
D000975:Antioxidants / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019255:NADPH Oxidases