NADPH oxidase-derived reactive oxygen species: involvement in vascular physiology and pathology.
Reactive oxygen species (ROS) are essential mediators of normal cell physiology. However, in the last few decades, it has become evident that ROS overproduction and/or alterations of the antioxidant system associated with inflammation and metabolic dysfunction are key pathological triggers of cardiovascular disorders. NADPH oxidases (Nox) represent a class of hetero-oligomeric enzymes whose primary function is the generation of ROS. In the vasculature, Nox-derived ROS contribute to the maintenance of vascular tone and regulate important processes such as cell growth, proliferation, differentiation, apoptosis, cytoskeletal organization, and cell migration. Under pathological conditions, excessive Nox-dependent ROS formation, which is generally associated with the up-regulation of different Nox subtypes, induces dysregulation of the redox control systems and promotes oxidative injury of the cardiovascular cells. The molecular mechanism of Nox-derived ROS generation and the means by which this class of molecule contributes to vascular damage remain debatable issues. This review focuses on the processes of ROS formation, molecular targets, and neutralization in the vasculature and provides an overview of the novel concepts regarding Nox functions, expression, and regulation in vascular health and disease. Because Nox enzymes are the most important sources of ROS in the vasculature, therapeutic perspectives to counteract Nox-dependent oxidative stress in the cardiovascular system are discussed.
"Petru Poni" Institute of Macromolecular Chemistry, 41A Grigore Ghica, Voda Alley, 700487 Iasi, Romania. adrian.manea@icbp.ro
Adrian
A
Manea
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D019255:NADPH Oxidases