EFFECT OF CONDITIONING OF BETA-MIGRATING VERY LOW-DENSITY-LIPOPROTEIN WITH MACROPHAGES ON THE ACCUMULATION OF CHOLESTERYL ESTERS IN SMOOTH-MUSCLE CELLS

The mechanism of cholesteryl ester accumulation in smooth muscle cells was investigated. Incubation of smooth muscle cells with beta-migrating very low-density lipoprotein (beta-VLDL, d < 1.006) for 24 h did not result in accumulation of oil red O-stained particles in the cells. However, incubation of smooth muscle cells with beta-VLDL in the presence of rat peritoneal macrophages induced accumulation of oil red O-stained granules in smooth muscle cells. Medium containing [H-3]-cholesteryl linoleate-labelled beta-VLDL ([H-3]beta-VLDL) that was conditioned with rat peritoneal macrophages increased the incorporation of [H-3]-cholesterol and the cholesteryl ester content in smooth muscle cells, whereas unconditioned [H-3]beta-VLDL did not. On zonal ultracentrifugation of conditioned medium containing [H-3]beta-VLDL with macrophages, radioactivity was found at two peaks of density 1.150 and < 1.006. This new fraction with d = 1.150 (peak II) migrated at beta-positions, the same as that of low-density lipoprotein (LDL) on agarose gel electrophoresis, and contained cholesteryl esters (28%), free cholesterol (15%) and phospholipid (43%). When smooth muscle cells were incubated with the peak II fraction. the radioactivity incorporated into smooth muscle cells and the cholesterol ester content of the cells increased. These results show that aortic smooth muscle cells in cooperation with macrophages can accumulate cholesteryl ester from beta-VLDL.