Enhanced macrophage degradation of biologically modified low density lipoprotein

Abstract

Low density lipoprotein (LDL) conditioned by incubation in the presence of rabbit aortic or human umbilical vein endothelial cells (endothelial cell-modified LDL) was degraded by macrophages three to five times more rapidly than LDL incubated in the absence of cells (control LDL). This enhanced degradation occurred mostly via a high affinity, saturable pathway related to the pathway for macrophage uptake of acetylated LDL. Conditioning LDL with cultured aortic smooth muscle cells had a qualitatively similar but smaller effect; conditioning with fibroblasts had no effect. Conditioning very low density lipoproteins or high density lipoproteins with endothelial cells did not affect subsequent metabolism of these lipoproteins by macrophages. Endothelial cell-modified LDL, while degraded more rapidly than control LDL by macrophages, was degraded more slowly by cultured smooth muscle cells and by human skin fibroblasts. Degradation of endothelial cell-modified LDL by macrophages was accompanied by stimulation of cholesterol esterification, inhibition of cholesterol synthesis, and a net increment in total cellular cholesterol content. Thus, a biologically generated modification of LDL is described that markedly alters cholesterol metabolism of macrophages and, consequently, may play a role in foam cell formation during atherogenesis.