Role of oxidative stress in atherosclerosis

The common risk factors for atherosclerosis increase production of reactive oxygen species (ROS) by endothelial, vascular smooth muscle, and adventitial cells. These ROS initiate processes involved in atherogenesis through several important enzyme systems, including xanthine oxidase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and nitric oxide synthase. also regulate vascular production of ROS. Oscillatory shear, which is present at sites where atherosclerosis develops, seems a particularly potent stimulus of superoxide production. The signaling cascade for activation of the NAD(P)H oxidase by angiotensin II has recently been elucidated and seems to involve a feed-forward mechanism that permits ongoing production of ROS for prolonged periods. Oxidative stress in humans with coronary artery disease is also exacerbated by a reduction of vascular extracellular superoxide dismutase, normally an important protective enzyme against the superoxide anion. (C) 2003 by Excerpta Medica, Inc.