STRETCH FORCE ON VASCULAR SMOOTH-MUSCLE CELLS ENHANCES OXIDATION OF LDL VIA SUPEROXIDE PRODUCTION

Hemodynamic forces on vasculature profoundly influence atherogenesis. mie examined the effect of stretch force on the oxidation of low-densi ty lipoprotein (LDL) by rat aortic smooth muscle cells (RASM) and supe roxide production. Stretch force was imposed on RASM cultured on defor mable dishes by stretching the dishes. Incubation of native LDL with s tatic RASM for 24 h resulted in LDL oxidation as indicated by increase s in thiobarbituric acid-reacting substances from 9.5 +/- 2.3 to 24.5 +/- 2.3 nmol malondialdehyde/mg. Stretch force on RASM augmented cell- mediated LDL oxidation to 149.3 +/- 17.1% concomitantly with increase in superoxide production. LDL oxidation was inhibited by superoxide di smutase or depletion of the metal ion in the culture medium, indicatin g that it was a metal ion-dependent and superoxide-mediated process. T he enhancement of LDL oxidation by stretch force was inhibited by diph enyliodonium, indicating the involvement of the NADH/NADPH oxidase sys tem. Our findings suggest that the increased oxidant stress induced by stretch force is one of the potential mechanisms whereby hypertension facilitates atherosclerosis.