Accumulation and mobilization of cholesteryl esters in cultured human fibroblasts exposed to free cholesterol-rich phospholipid vesicles.

The uptake of free cholesterol (FC) into cells by surface transfer and its esterification to cholesteryl esters (CE) has been studied with a system of FC-egg phosphatidylcholine (EPC) vesicles and human lung fibroblasts in serum-free growth medium. The influx of FC was dependent on the molar ratio of FC to EPC in the donor vesicles. The FC incorporated by surface transfer was available for esterification in the cells. Incubations with FC/EPC vesicles with a FC/EPC molar ratio of 0.5: 1 gave a small net decrease in cellular CE, while 1:1 vesicles gave a mild increase. When the cells were incubated with 2:1 FC/EPC vesicles an extensive accumulation of CE was demonstrated, which was accentuated if albumin was present in the medium. The CE accumulated in the form of lipid droplets within the cells. The largest of these droplets exhibited positive birefringence with formée crosses, that is typical for liquid crystals of cholesteryl esters. If cells loaded with CE were incubated with vesicles with low FC/EPC ratios a net efflux of CE was noted. The present study demonstrates that the uptake of FC from lipid vesicles by surface transfer can reproduce typical features of foam cells in early atherosclerosis.