Journal of Lipid Research, Vol 21, 970-980, Copyright © 1980 by Lipid Research, Inc.

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Cholesteryl ester synthesis in macrophages: stimulation by beta-very low density lipoproteins from cholesterol-fed animals of several species

RW Mahley, TL Innerarity, MS Brown, YK Ho and JL Goldstein

Animals fed cholesterol accumulate several types of cholesterol-rich lipoproteins in their plasma and ultimately develop cholesteryl ester deposition in tissue macrophages. Previous studies in the cholesterol- fed dog have shown that one class of cholesterol-rich lipoproteins. beta-migrating very low density lipoproteins (beta-VLDL, density < 1.006 g/ml), possesses a unique ability to produce cellular cholesteryl ester accumulation when incubated with mouse peritoneal macrophages in vitro. This accumulation results from the receptor-mediated uptake of beta-VLDL with subsequent lysosomal hydrolysis of the lipoprotein and re-esterification of the liberated cholesterol. In the current studies, we demonstrate that beta-VLDL obtained from cholesterol-fed animals of several other species, including monkeys, rabbits, and rats, also causes cholesteryl ester accumulation in monolayers of mouse peritoneal macrophages, as monitored by an increase in the rate at which the cells incorporate exogenous [14C]oleate into cholesteryl [14C]oleate. Like canine beta-VLDL, the beta-VLDL from these three other species were effective at low concentrations and exhibited saturation kinetics, suggesting that they, too, entered macrophages by receptor-mediated endocytosis. Very low density lipoprotein (VLDL) from normal animals and low density lipoprotein (LDL) from normal and cholesterol-fed monkeys, rats, and rabbits did not stimulate cholesteryl ester synthesis in mouse peritoneal macrophages. In addition to their effects on mouse macrophages, the beta-VLDL from cholesterol-fed dogs and rabbits stimulated cholesteryl ester synthesis in cultured human monocytes. The current findings suggest that beta-VLDL from cholesterol- fed animals has the general property of stimulating cholesteryl ester synthesis and accumulation in macrophages.
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