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(Circulation Research. 2000;87:1074.)
© 2000 American Heart Association, Inc.

Editorial

The Oxidative Paradox

Another Piece in the Puzzle

Cam Patterson, Nageswara R. Madamanchi, Marschall S. Runge

From the University of North Carolina at Chapel Hill, Program in Molecular Cardiology, Division of Cardiology and Department of Medicine (C.P., N.R.M., M.S.R.) and Lineberger Comprehensive Cancer Center (C.P.), Chapel Hill, NC.

Correspondence to Marschall S. Runge, MD, PhD, Chairman, Department of Medicine, University of North Carolina at Chapel Hill, 3033 Old Clinic Building, Campus Box 7005, Chapel Hill, NC 27599-7005. E-mail mrunge@med.unc.edu

Key Words: atherosclerosis • oxidantstress • vascularbiology

	Introduction

 
Because atherosclerosis is a disease of many risk factors, a complex pathology, and diverse clinical manifestations, the as yet unattained Holy Grail of atherosclerosis research is a unifying pathway to explain its many aspects and provide a single point at which to measure risk or intervene in its clinical course. If vascular biology possesses such a relic, it would have many of the characteristics attributed to oxidative stress. Risk factors for atherosclerosis, such as hypertension¹ and hyperlipidemia,² are potent stimuli for the generation of reactive oxygen species (ROS) in experimental systems, and it is likely that cigarette smoking and diabetes mellitus share oxidative heritages. At the molecular level, signaling in response to proatherogenic agents, such as -thrombin,³ platelet-derived growth factor,⁴ and angiotensin II,^{5 6} requires the generation of ROS via oxidase systems. In fact, many of the hallmarks of atherosclerosis, including endothelial dysfunction, smooth muscle cell (SMC) proliferation, and inflammatory recruitment, occur in response to ROS. In this issue of Circulation Research, Schieffer et al⁷ contribute to our understanding of these events by demonstrating that angiotensin II–induced cytokine activation via the Janus kinase/signal transducer and activator of transcription (STAT) pathway requires oxidant generation by the NAD(P)H oxidase in SMCs. Their data are consistent with the notion that ROS are central mediators of adverse events in atherosclerosis. The oxidative paradox, then, is the inability of clinical investigators to definitively demonstrate that modulation of ROS by the use of antioxidant therapies has any effect on atherogenesis.

Angiotensin II is the best-characterized stimulus . . . [Full Text of this Article]

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