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(Circulation Research. 2000;86:365.)
© 2000 American Heart Association, Inc.

Editorials

How Could a Genetic Variant of the p22^phox Component of NAD(P)H Oxidases Contribute to the Progression of Coronary Atherosclerosis?

Michael S. Wolin

From the Department of Physiology, New York Medical College, Valhalla, NY.

Correspondence to Michael S. Wolin, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail mike_wolin@nymc.edu

Key Words: atherosclerosis • coronary artery disease • NAD(P)H oxidase • oxidant stress • redox signaling

	Introduction

 
Reactive O₂ species (ROS) are thought to contribute to the progression of atherosclerotic coronary artery disease (CAD).^{1 2} In this issue of Circulation Research, Cahilly and colleagues³ provide data supporting an association between a histidine⁷² to tyrosine mutation at the potential site for heme binding of the p22^phox subunit of NAD(P)H oxidases and increased severity and progression of CAD in patients from the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Although it was previously shown that the p22^phox subunit of NAD(P)H oxidases is increased in atherosclerotic human coronary arteries,⁴ its precise role, if any, in disease pathogenesis and the impact of this mutation on the function of NAD(P)H oxidases remain to be elucidated. Given that the p22^phox subunit is a component of both the phagocytic cell oxidase and NAD(P)H oxidases in other cell types in the vessel wall, the mutation could affect the production of ROS and multiple signaling systems that influence the progression of CAD.

The best understood oxidase containing p22^phox is the NADPH oxidase of phagocytic cells (eg, neutrophils and macrophages), which are known to contribute to the development and progression of atherosclerotic vascular disease. Activation of these phagocytic cells causes the cytosolic p47^phox, p67^phox, and p40^phox subunits and the G-protein rac-2 to bind with the membrane-bound flavohemoprotein gp91^phox and p22^phox subunits, producing the superoxide anion (O₂^·-)–generating form of the NADPH oxidase.⁵ The high capacity for O₂^·- production, together with the ability of phagocytes to generate ROS and nitric oxide–derived reactive species, including hypochlorous acid, chloramines, . . . [Full Text of this Article]

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