Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis.

Abstract

Major reactive oxygen species (ROS)-producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking enhance ROS generation and decrease endothelial NO production. Key molecular events in atherogenesis such as oxidative modification of lipoproteins and phospholipids, endothelial cell activation, and macrophage infiltration/activation are facilitated by vascular oxidative stress and inhibited by endothelial NO. Atherosclerosis develops preferentially in vascular regions with disturbed blood flow (arches, branches, and bifurcations). The fact that these sites are associated with enhanced oxidative stress and reduced endothelial NO production is a further indication for the roles of ROS and NO in atherosclerosis. Therefore, prevention of vascular oxidative stress and improvement of endothelial NO production represent reasonable therapeutic strategies in addition to the treatment of established risk factors (hypercholesterolemia, hypertension, and diabetes mellitus).

• Authors: Ulrich Förstermann, Ning Xia, Huige Li
• Journal: Circulation research (Circ Res) Vol. 120 Issue 4 Pg. 713-735 (Feb 17 2017) ISSN: 1524-4571 [Electronic] United States
• PMID: 28209797 (Publication Type: Journal Article, Review)
• Copyright: © 2017 American Heart Association, Inc.

Chemical References

• Reactive Oxygen Species
• Nitric Oxide
• Nitric Oxide Synthase Type III

Topics

• Animals
• Atherosclerosis (genetics, metabolism, pathology)
• Endothelium, Vascular (metabolism, pathology)
• Humans
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress (physiology)
• Reactive Oxygen Species (metabolism)
• Species Specificity