Macrophages enhance binding of beta-VLDL and cholesterol ester accumulation in cultured aortic smooth muscle cells.

Abstract

The effect of macrophages on the uptake of beta-very low-density lipoprotein (beta-VLDL) by smooth muscle cells (SMC) expressing different morphological phenotypes was examined in culture. The SMC were grown alone and in co-culture with macrophages for four days, then incubated with different concentrations of 125I-beta-VLDL for 3 h at 4 degrees C or with 75 ug/ml beta-VLDL for 24 h at 37 degrees C. The binding of beta-VLDL to SMC at 4 degrees C was enhanced in the presence of macrophages irrespective of the phenotype expressed by SMC. This occurred through modification of the lipoprotein, since binding of re-isolated macrophage-conditioned beta-VLDL to SMC was 12.5 times that of fresh beta-VLDL. This modified form of beta-VLDL competed with fresh beta-VLDL for binding to SMC. Binding was inhibited in the presence of probucol, suggesting that an oxidative mechanism may be involved. The presence of macrophages also enhanced the accumulation of beta-VLDL-derived cholesterol in SMC. While most of this is a consequence of the enhanced binding, macrophages may also act directly on SMC to increase cholesterol accumulation, since the activity of acid cholesterol ester hydrolase and neutral cholesterol ester hydrolase in SMC was reduced in the presence of macrophages.