Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:29-38
Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150649.39934.13
Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150649.39934.13
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© 2005 American Heart Association, Inc.
Brief Reviews |
Oxidative Stress and Vascular Disease
From the Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill.
Correspondence to Marschall S. Runge, MD, PhD, Department of Medicine, 3033 Old Clinic Bldg., University of North Carolina, Chapel Hill, NC 27599-7005. E-mail mrunge{at}med.unc.edu
Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases (CVD). These ROS can be released from nicotinamide adenine dinucleotide (phosphate) oxidase, xanthine oxidase, lipoxygenase, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis: from the initiation of fatty streak development through lesion progress to ultimate plaque rupture. Various animal models of oxidative stress support the notion that ROS have a causal role in atherosclerosis and other cardiovascular diseases. Human investigations also support the oxidative stress hypothesis of atherosclerosis. Oxidative stress is the unifying mechanism for many CVD risk factors, which additionally supports its central role in CVD. Despite the demonstrated role of antioxidants in cellular and animal studies, the ineffectiveness of antioxidants in reducing cardiovascular death and morbidity in clinical trials has led many investigators to question the importance of oxidative stress in human atherosclerosis. Others have argued that the prime factor for the mixed outcomes from using antioxidants to prevent CVD may be the lack of specific and sensitive biomarkers by which to assess the oxidative stress phenotypes underlying CVD. A better understanding of the complexity of cellular redox reactions, development of a new class of antioxidants targeted to specific subcellular locales, and the phenotype-genotype linkage analysis for oxidative stress will likely be avenues for future research in this area as we move toward the broader use of pharmacological and regenerative therapies in the treatment and prevention of CVD.
Antioxidants are ineffective in reducing cardiovascular death despite evidence for oxidative stress (OS) in cardiovascular diseases (CVD) from animal and human investigations. A better understanding of cellular redox reactions, development of targeted antioxidants and phenotype-genotype linkage analysis for OS are necessary for broader use of pharmacological and regenerative therapies for CVD.
Key Words: reactive oxygen species • NAD(P)H oxidase • mitochondria • atherosclerosis • antioxidants
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