Induction of antioxidant stress proteins in vascular endothelial and smooth muscle cells: Protective action of vitamin C against atherogenic lipoproteins

Elevated levels of lipid peroxidation and increased formation of reactive o xygen species within the vascular wall in atherosclerosis can overwhelm cel lular antioxidant defence mechanisms. Accumulating evidence implicates oxid atively modified low density lipoproteins (LDL) in vascular dysfunction in atherosclerosis and oxidized LDL have been localized with in atheroscleroti c lesions. We here report that human oxidatively modified LDL induce expres sion of 'anti-oxidant-like' stress proteins in vascular cells, involving in creases in the activity of L-cystine transport, glutathione synthesis, heme oxygenase-1 and the murine stress protein MSP23. Moreover, treatment of hu man arterial smooth muscle cells with the dietary antioxidant vitamin C mar kedly attenuates adaptive increases in endogenous antioxidant gene expressi on and affords protection against smooth muscle cell apoptosis induced by m oderately oxidized LDL. As vascular cell death is a key feature of atherosc lerotic lesions and may contribute to the plaque 'necrotic' core, cap ruptu re and thrombosis, our findings suggest that the cytoprotective actions of vitamin C could Limit plaque instability in advanced atherosclerosis.