Background—To explore the role of intracellular oxidative stress in high glucose–induced atherogenesis, we examined the effect of probucol and/or α-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 α-tocopherol significantly suppressed high glucose–induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and α-tocopherol suppressed high glucose–induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, α-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, α-tocopherol, suramin, and calphostin C.
Conclusions—These findings suggest that probucol and α-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.