OXIDIZED LOW-DENSITY-LIPOPROTEIN STIMULATES COLLAGEN PRODUCTION IN CULTURED ARTERIAL SMOOTH-MUSCLE CELLS

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth mus cle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 mu g/ ml of human LDL with/without 5 mu M Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of H-3-proline-labeled collagenous protein. Ox idation of LDL was evaluated by electrophoresis and by the level of th iobarbituric acid reactive substances (TEARS). Ascorbic acid reduced t he oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbi c acid, no differences were noted in collagen production between LDL a nd LDL + Cu2+. Without ascorbic acid, collagen production with LDL + C u2+ was increased dose-dependently up to 6-fold with 150 mu g/ml LDL, while no such effects were observed at any doses of native LDL. The ad dition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed o xidation (88% reduction), and significantly reduced collagen productio n close to that seen with native LDL. These results indicate that oxid ized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating co llagen production in SMCs, which could lead to collagenosis in atheros clerosis.