Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets.

Abstract

NADPH oxidases are a family of enzymes that generate reactive oxygen species (ROS). The NOX1 (NADPH oxidase 1) and NOX2 oxidases are the major sources of ROS in the artery wall in conditions such as hypertension, hypercholesterolaemia, diabetes and ageing, and so they are important contributors to the oxidative stress, endothelial dysfunction and vascular inflammation that underlies arterial remodelling and atherogenesis. In this Review, we advance the concept that compared to the use of conventional antioxidants, inhibiting NOX1 and NOX2 oxidases is a superior approach for combating oxidative stress. We briefly describe some common and emerging putative NADPH oxidase inhibitors. In addition, we highlight the crucial role of the NADPH oxidase regulatory subunit, p47phox, in the activity of vascular NOX1 and NOX2 oxidases, and suggest how a better understanding of its specific molecular interactions may enable the development of novel isoform-selective drugs to prevent or treat cardiovascular diseases.

• Authors: Grant R Drummond, Stavros Selemidis, Kathy K Griendling, Christopher G Sobey
• Journal: Nature reviews. Drug discovery (Nat Rev Drug Discov) Vol. 10 Issue 6 Pg. 453-71 (Jun 2011) ISSN: 1474-1784 [Electronic] England
• PMID: 21629295 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antioxidants
• Membrane Glycoproteins
• Reactive Oxygen Species
• NADH, NADPH Oxidoreductases
• CYBB protein, human
• NADPH Oxidase 1
• NADPH Oxidase 2
• NADPH Oxidases

Topics

• Animals
• Antioxidants (administration & dosage)
• Drug Delivery Systems (methods)
• Humans
• Membrane Glycoproteins (antagonists & inhibitors, metabolism)
• NADH, NADPH Oxidoreductases (antagonists & inhibitors, metabolism)
• NADPH Oxidase 1
• NADPH Oxidase 2
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects, physiology)
• Reactive Oxygen Species (metabolism)
• Vascular Diseases (drug therapy, enzymology)