Regulation of cholesterol synthesis and esterification in primary cultures of macrophages following uptake of chylomicron remnants

The effects of chylomicron remnants (CR), beta-very-low-density-lipoproteins (beta-VLDL) and low-density-lipoproteins (LDL) on intracellular cholesterol synthesis and esterification in primary rabbit macrophages was determined by assaying for HMG-CoA reductase activity and cholesterol esterification. At physiological cholesterol concentrations, both CR and LDL inhibited cholesterol synthesis by almost 60% while beta-VLDL was less potent achieving only 30% inhibition. Cholesterol esterification rates were increased four-fold by CR and LDL, whereas beta-VLDL increased esterification 14 times above controls. Qualitatively, the effect of CR on cholesterol synthesis and esterification in rabbit macrophages differs from observations in transformed macrophage cells. Quantitatively, the enhanced rates of cholesterol esterification and weak inhibition of cholesterol synthesis following beta-VLDL uptake may explain why this lipoprotein rapidly induces foam cell formation in vitro.