Metabolism of atherogenic lipoproteins by smooth muscle cells of different phenotype in culture.

Smooth muscle cells of the rabbit aorta, when grown in vitro, express three distinguishable forms of phenotype (contractile, reversible synthetic, and irreversible synthetic). We compared the interactions of these three smooth muscle phenotypes with rabbit very low density lipoprotein (VLDL), low density lipoprotein (LDL), and very low density lipoprotein from cholesterol-fed rabbits (beta-VLDL). beta-VLDL showed saturable. high-affinity binding characteristics with each phenotype predominantly through the B/E receptor. The irreversible synthetic cells displayed the greatest binding capacity and the contractile cells, the least. Binding and degradation of normal VLDL was less than that of beta-VLDL and higher than that of LDL. Only the irreversible synthetic cells showed substantial (about threefold) cholesteryl ester formation and cholesterol accumulation, and then only when incubated with beta-VLDL. Substantial stainable lipid, shown chemically to include triglyceride, cholesterol and cholesteryl ester, was also observed only when irreversible synthetic cells were exposed to beta-VLDL. The high capacity of irreversible synthetic-state, smooth muscle cells to bind and accumulate beta-VLDL in contrast to the relative immunity of contractile cells may be relevant to the genesis of atherosclerosis in the rabbit and possibly also in humans.