NADPH Oxidases: Functions and Pathologies in the Vasculature

• Type of Material: Article
• Authors: Bernard P Lassegue, Emory University; Kathy Griendling, Emory University
• Language: English
• Date: 2010-04
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 American Heart Association, Inc. All rights reserved.
• Final Published Version (URL): http://atvb.ahajournals.org/content/30/4/653
• Title of Journal or Parent Work: Arteriosclerosis, Thrombosis, and Vascular Biology
• ISSN: 1079-5642
• Volume: 30
• Issue: 4
• Start Page: 653
• End Page: 661
• Grant/Funding Information: This work was supported by National Institutes of Health Grants HL38206, HL058863 and HL095070.; National Heart, Lung, and Blood Institute : NHLBI
• Keywords: Hypertension; NADPH oxidase; Blood Vessels; Reactive Oxygen Species; Atherosclerosis
• Research Categories: Health Sciences, Pathology

Abstract

Reactive oxygen species (ROS) are ubiquitous signaling molecules in biological systems. Four members of the NADPH oxidase (Nox) enzyme family are important sources of ROS in the vasculature: Nox1, Nox2, Nox4 and Nox5. Signaling cascades triggered by stresses, hormones, vasoactive agents and cytokines control the expression and activity of these enzymes and of their regulatory subunits, among which p22phox, p47phox, Noxa1 and p67phox are present in blood vessels. Vascular Nox enzymes are also regulated by Rac, ClC-3, Poldip2 and PDI. Multiple Nox subtypes, simultaneously present in different subcellular compartments, produce specific amounts superoxide, some of which is rapidly converted to hydrogen peroxide. The identity and location of these ROS, and of the enzymes that degrade them, determine their downstream signaling pathways. Nox enzymes participate in a broad array of cellular functions including differentiation, fibrosis, growth, proliferation, apoptosis, cytoskeletal regulation, migration and contraction. They are involved in vascular pathologies such as hypertension, restenosis, inflammation, atherosclerosis and diabetes. As our understanding of the regulation of these oxidases progresses, so will our ability to alter their functions and associated pathologies.