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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1332.)
© 2005 American Heart Association, Inc.

Brief Reviews

Oxidative Enzymopathies and Vascular Disease

Jane A. Leopold; Joseph Loscalzo

From Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Joseph Loscalzo, MD, PhD, Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany Street, CABR W-507, Boston, MA 02118. E-mail jloscalz{at}bu.edu

Series Editor: Kathy K. Griendling
ATVB In Focus Redox Mechanisms in Blood Vessels

Previous Brief Reviews in this Series:

•Mueller CFH, Laude K, McNally JS, Harrison DG. Redox mechanisms in blood vessels. 2005;25:274–278.
•Gutterman DD, Miura H, Liu Y. Redox modulation of vascular tone: focus of potassium channel mechanisms of dilation. 2005;25:671–678.
•Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. 2005;25:1102–1111.

In the vasculature, reactive oxygen species (ROS) generated by both mitochondrial respiration and enzymatic sources serve as integral components of cellular signaling and homeostatic mechanisms. Because ROS are highly reactive biomolecules, the cellular redox milieu is carefully maintained by small-molecule antioxidants and antioxidant enzymes to prevent the deleterious consequences of ROS excess. When this redox balance is perturbed, because of either increased ROS production or decreased antioxidant capacity, oxidant stress is increased in the vessel wall and, if not offset, vascular dysfunction ensues. A number of heritable polymorphisms of pro-oxidant enzymes, including 5-lipoxygenase, cyclooxygenase-2, nitric oxide synthase-3, and NAD(P)H oxidase, have been identified and found to modulate ROS production and, thereby, the risk of atherothrombotic cardiovascular disease in individuals with these genetic polymorphisms. Similarly, heritable deficiency of the antioxidant enzymes catalase, glutathione peroxidases, glutathione-S-transferases, heme oxygenase, and glucose-6-phosphate dehydrogenase favors ROS accumulation, and has been associated with an increased risk of vascular disease. Individually, each of these polymorphisms imposes a state of uncompensated oxidant stress on the vasculature and collectively comprise the oxidative enzymopathies.

Heritable polymorphisms of pro-oxidant enzymes and antioxidant enzyme deficiencies modulate the risk of atherothrombotic cardiovascular disease. Individually, inheritance of one of these polymorphisms or enzyme deficiencies promotes a state of uncompensated oxidant stress on the vasculature. Collectively, these enzymes polymorphisms and deficiencies are recognized as the oxidative enzymopathies.

Key Words: antioxidants • atherosclerosis • genetic polymorphism • reactive oxygen species

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