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(Circulation. 1999;99:1370-1378.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Antioxidants Improve Impaired Insulin-Mediated Glucose Uptake and Prevent Migration and Proliferation of Cultured Rabbit Coronary Smooth Muscle Cells Induced by High Glucose

Kenichi Yasunari, MD; Masakazu Kohno, MD; Hiroaki Kano, MD; Koji Yokokawa, MD; Mieko Minami, MD; Junichi Yoshikawa, MD

From the First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.

Correspondence to Kenichi Yasunari, MD, The First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545-8586, Japan.

Background—To explore the role of intracellular oxidative stress in high glucose–induced atherogenesis, we examined the effect of probucol and/or -tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs).

Methods and Results—Chronic high-glucose-medium (22.2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB–mediated VSMC migration, [³H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and -tocopherol significantly suppressed high glucose–induced increase in VSMC migration, cell number, and [³H]thymidine incorporation. Probucol and -tocopherol suppressed high glucose–induced elevation of the cytosolic ratio of NADH/NAD⁺, phospholipase D, and membrane-bound protein kinase C activation. Probucol, -tocopherol, and calphostin C improved the high glucose–induced suppression of insulin-mediated [³H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, -tocopherol, suramin, and calphostin C.

Conclusions—These findings suggest that probucol and -tocopherol may suppress high glucose–induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD⁺, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.

Key Words: antioxidants • muscle, smooth • phospholipase • protein kinase • insulin

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