title: Reactive oxygen species and endothelial function--role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases.
abstract: The healthy endothelium prevents platelet aggregation and leucocyte adhesion, controls permeability to plasma components and maintains vascular integrity. Damage to the endothelium promotes endothelial dysfunction characterized by: altered endothelium-mediated vasodilation, increased vascular reactivity, platelet aggregation, thrombus formation, increased permeability, leucocyte adhesion and monocyte migration. Molecular processes contributing to these phenomena include increased expression of adhesion molecules, synthesis of pro-inflammatory and pro-thrombotic factors and increased endothelin-1 secretion. Decreased nitric oxide bioavailability and increased generation of reactive oxygen species (ROS) are among the major molecular changes associated with endothelial dysfunction. A critical source of endothelial ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, including the prototypic Nox2-based NADPH oxidases, Nox1, Nox4 and Nox5. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase and uncoupled nitric oxide synthase (NOS). Cross-talk between ROS-generating enzymes, such as mitochondrial oxidases and Noxs, is increasingly implicated in cellular ROS production. The present review discusses the importance of endothelial ROS in health and disease and focuses on the major ROS-generating systems in the endothelium, namely uncoupled endothelial nitric oxide synthase and NADPH oxidases.
authors: Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada.
authors: Augusto C
authors: AC
authors: Montezano
authors: Rhian M
authors: RM
authors: Touyz
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014652:Vascular Diseases / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D007527:Isoenzymes; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases