PROLIFERATIVE AND CYTOTOXIC EFFECTS OF MILDLY OXIDIZED LOW-DENSITY LIPOPROTEINS ON VASCULAR SMOOTH-MUSCLE CELLS

We have investigated the role of low-density lipoprotein (LDL) oxidati on in the proliferative effect of LDLs on cultured bovine aortic smoot h-muscle cells and compared it with their effect on bovine aortic endo thelial cells. The following conclusions were reached. (1) Non-toxic d oses of mildly oxidized LDLs elicit a proliferative effect on smooth-m uscle cells significantly higher than that of native LDLs or lipoprote in-depleted serum. The proliferative effect is dependent on time (rela tively slow), dose (high doses are cytotoxic) and the level of LDL oxi dation. (2) The proliferative effect on smooth-muscle cells is counter balanced at high concentrations of mildly oxidized LDLs (or at high ox idation levels) by their cytotoxic effect. (3) The same dose of mildly oxidized LDLs exhibits no proliferative effect on endothelial cells b ut rather a cytotoxic one. Endothelial cells may therefore be intrinsi cally more susceptible to the cytotoxic effect of mildly oxidized LDLs than are smooth-muscle cells. (4) The proliferative effect of native LDLs on smooth-muscle cells results (at least in part) from cell-induc ed LDL oxidation during cell culture as suggested by (i) the progressi ve LDL oxidation over the 3 days of contact between LDLs and smooth-mu scle cells and (ii) the concomitant inhibition of LDL oxidation and pr oliferative effect by butylated hydroxytoluene. The hypothetical mecha nisms and potential involvement in atherogenesis are discussed.