doi: 10.1161/hq0901.095550
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Expression of Glutaredoxin in Human Coronary Arteries
Its Potential Role in Antioxidant Protection Against Atherosclerosis
From the Division of Cardiovascular and Respiratory Medicine, Departments of Internal Medicine (M.O., N.I., T.S., Y.S., K.-i.H., S.K., M.Y.) and Surgical Pathology (H.A., Y.H., H.I.), Kobe University Graduate School of Medicine, Kobe, and the Department of Biological Response (J.Y.), Institute for Virus Research, Kyoto University, Kyoto, Japan.
Correspondence to Nobutaka Inoue, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, chuo-ku, Kobe, 650-0017, Japan. E-mail nobutaka{at}med.kobe-u.ac.jp
Abstract—— Oxidative stress is considered an important factor in atherogenesis. Mammalian cells have a complex network of antioxidants such as catalase, superoxide dismutase, and glutathione peroxidase. However, the mechanisms that regulate the cellular redox state in the vessel wall remain unclear. Recent study has shown that thioredoxin, a thiol-disulfide oxidoreductase, is expressed in atherosclerotic plaques of human carotid arteries. In this study, we investigated the localization and expressional change of glutaredoxin and thioredoxin, two important members of the thiol-disulfide oxidoreductases, in autopsy samples of human coronary arteries. In nonatherosclerotic coronary arteries, glutaredoxin was expressed in endothelial cells, in fibroblasts of the adventitia, and most intensely in medial smooth muscle cells. Interestingly, in atherosclerotic lesions such as hypercellular lesions, the infiltrating macrophages highly expressed glutaredoxin. The expressional pattern of thioredoxin was quite similar to that of glutaredoxin. Western blot analysis demonstrated that hydrogen peroxide stimulated the expression of glutaredoxin in a time- and dose-dependent manner in cultured human coronary artery smooth muscle cells. Fluorescence microtopography with dihydroethidium demonstrated that the generation of reactive oxygen species was associated with the expression of glutaredoxin. These results suggest the possible involvement of thiol-disulfide oxidoreductases in antioxidant protection in human coronary arteries.
Key Words: antioxidants • atherosclerosis • coronary artery disease • free radicals
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