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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1912-1917.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Overexpression of Human Catalase Gene Decreases Oxidized Lipid-Induced Cytotoxicity in Vascular Smooth Muscle Cells

Nalini Santanam; Nathalie Augé; Mimi Zhou; Channa Keshava; Sampath Parthasarathy

From the Department of Gynecology and Obstetrics, Emory University, Atlanta, Ga.

Correspondence to Sampath Parthasarathy, PhD, Department of Gynecology and Obstetrics, Emory University, School of Medicine, 1639 Pierce Dr, 4302 WMB, Atlanta, GA 30322. E-mail spartha{at}emory.edu

Abstract—Reactive oxygen metabolites such as hydrogen peroxide (H₂O₂) and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of various diseases including atherosclerosis. The effects of these oxidants could be inhibited by the external addition of an antioxidant, suggesting the promotion or propagation of further oxidation. In this study, we describe the stable overexpression of human catalase in smooth muscle cells and the resistance of these cells to cytotoxicity induced not only by the addition of H₂O₂ but also by the addition of 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results pose an intriguing possibility of the generation of H₂O₂ from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H₂O₂. To explain the observed results by which catalase could overcome the effects of 13-HPODE, we propose that oxidized fatty acids are degraded in the cellular peroxisomes, resulting in the generation of H₂O₂. In other words, the cellular effects of peroxidized fatty acids could be attributed to the generation of H₂O₂.

Key Words: atherosclerosis • 13-HPODE • peroxisomes • hydrogen peroxide • ß-oxidation

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