Vascular oxidant stress: Molecular mechanisms and pathophysiological implications

Abstract

The term oxidative stress refers to a situation in which cells are exposed to excessive levels of either molecular oxygen or chemical derivatives of oxygen (ie, reactive oxygen species). Three enzyme systems produce reactive oxygen species in the vascular wall: NADH/NADPH oxidase, xanthine oxidoreductase, and endothelial nitric oxide synthase. Among vascular reactive oxygen species superoxide anion plays a critical role in vascular biology because it is the source for many other reactive oxygen species and various vascular cell functions. It is currently thought that increases in oxidant stress, namely excessive production of superoxide anion, are involved in the pathophysiology of endothelial dysfunction that accompanies a number of cardiovascular risk factors including hypercholesterolemia, hypertension and cigarette smoking. On the other hand, vascular oxidant stress plays a pivotal role in the evolution of clinical conditions such as atherosclerosis, diabetes and heart failure.

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…There are two major markers of hypertension, endothelial cell dysfunction and vascular smooth muscle cell hypertrophy. These changes are due to an increase in oxidative stress and linked with decreased NO availability (Zalba et al 2000). The reduction in nitric oxide availability is tied to increased O 2 ·-levels, mainly contributed by NADPH oxidase in smooth muscle cells, resulting in NO intereaction with O 2 ·-and the formation of peroxynitrite (ONOO -, (Landmesser et al 2002;Rathaus et al 2002).…”

Atherosclerotic Vascular Disease Conference

“…53 Important sources of ROS are vascular smooth muscle cells, endothelial cells, fibroblasts, and infiltrating leukocytes. 55 Production of ROS affects gene transcription, damages DNA, and increases production of inflammatory transcription factors. 56 The 2 best-characterized effects include oxidation of LDL and scavenging of endothelium-derived NO.…”

Functional Consequences of Endothelial Nitric Oxide Synthase Uncoupling in Congestive Cardiac Failure

“…Diminished expression and activity of endothelial nitric oxide synthase (eNOS) and enhanced NO biodegradation by vascular superoxide (O 2 ·Ϫ ) in CCF decreases NO bioavailability. 2 O 2 ·Ϫ and NO react rapidly to produce peroxynitrite, 3 which further decreases NO bioavailability while promoting protein and lipid oxidation. 4 CCF is associated with increased levels of oxygen-derived free radicals, 2,5 in particular O 2 ·Ϫ produced by xanthineoxidase, cyclooxygenase, and mitochondrial oxidases, 6,7 with vascular NAD(P)H oxidases being the principal source in CCF.…”