Oxidized LDL induces an increase in the relative collagen synthesis of rabbit aortic smooth muscle cells

Cell degeneration and collagenosis are the main features in atherosclerotic plaque. We examined the effects of human low density lipoprotein (LDL) on cultured rabbit aortic smooth muscle cells (SMCs). Copper oxidized LDL (LDL+Cu) injured the SMCs more than did native LDL. Cytotoxicity of oxidized LDL was prevented by the simultaneous addition of butylated hydroxytoluene (BHT) and ethylenediamine tetraacetic acid. Collagen synthesis increased up to 6 fold after incubation with 200 micrograms protein/ml of both native and oxidized LDL compared with that incubated in bovine serum albumin. Noncollagen protein synthesis was significantly reduced by oxidized LDL when compared to that by native LDL. Therefore, oxidized LDL increased the relative collagen synthesis (3.33%) to a greater extent than did native LDL (0.72%). By adding BHT to LDL+Cu, the elevated relative collagen synthesis was reversed due to the restoration of noncollagen protein synthesis while it also inhibited LDL peroxidation as evaluated by the formation of malondialdehyde (MDA). However, sodium MDA (up to 200 microM) did not induce either cytotoxicity or an increase of relative collagen synthesis. We therefore conclude that oxidized human LDL enhanced the relative collagen synthesis coinciding with the induction of injury in cultured aortic SMCs, however free MDA may not be the component responsible for these effects.