Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins

Abstract

Human low density lipoprotein (LDL) was incubated with an established line of rabbit aortic endothelial cells. Density gradient fractionation showed a time-, concentration-, and temperature-dependent increase in the average density of the LDL (from about 1.036 to as high as 1.070 g/ml). Incubation without cells or with other types of cultured cells (fibroblasts, hepatocytes, 3T3-L1 cells) caused no significant change in density. 125I-Labeled LDL (125I-LDL) recovered after incubation with endothelial cells (EC-modified LDL) was taken up and degraded 3 to 4 times more rapidly than control LDL by resident mouse peritoneal macrophages and by an established tumor line of mouse macrophages (J774 cells). Macrophage degradation of EC-modified 125I-LDL exhibited saturation kinetics (greater than 85% inhibited by excess unlabeled EC-modified LDL). Degradation was also inhibited by unlabeled acetylated LDL and, conversely, unlabeled EC-modified LDL inhibited degradation of acetylated 125I-LDL. Incubation of LDL with conditioned medium-removed from endothelial cell cultures modified neither its density nor its rate of degradation by macrophages. These studies show that endothelial cells have the potential to metabolically modify the LDL molecule, generating a form that is more rapidly degraded by macrophages and that is recognized by the macrophage receptor for acetylated LDL. This process may play a significant role in the pathogenesis of atherosclerosis.