Very low density lipoproteins stimulate cholesteryl ester formation in U937 macrophages. Heterogeneity and biologic variation among normal humans.

Abstract

Normolipidemic fasting VLDL stimulated the formation of cholesteryl ester in the human macrophage-like cell line, U937. VLDL from different persons exhibited heterogeneity over a 10-fold range in stimulating cholesterol esterification, and were 7% to 98% as active as human LDL. The effects of VLDL in U937 cells were highly correlated to those in normal human fibroblasts. VLDL did not induce cholesterol esterification in resident mouse peritoneal macrophages, nor in fibroblasts that lacked LDL receptors, suggesting that receptors for LDL, rather than for beta-VLDL, mediate the effects of VLDL. The active VLDL particles were found in the dense VLDL subfraction, Sf20 to 60, but not in Sf60 to 100 or Sf100 to 400. The activity of unfractionated VLDL was correlated directly with % cholesteryl ester in total or Sf20 to 60 VLDL, and inversely with VLDL triglycerides. Biologic variation of fasting VLDL activity in U937 cells was found in 13 normolipidemic ambulatory subjects. As compared to the correlation between the activity of two VLDL samples derived from a single aliquot of blood (r = 0.90), the correlation was lower (r = 0.60) between the activity of samples taken on successive days, and even less (r = 0.05) between VLDL samples obtained 2 weeks apart. Substantial biologic variation also occurred in VLDL composition except for VLDL unesterified cholesterol. These findings suggest an environmental influence on VLDL metabolism by macrophages.