The High-Density Lipoprotein Receptor

Abstract

An early characteristic of developing atherosclerotic lesions is the accumulation of cells in the artery wall that contain numerous lipid droplets comprised mostly of cholesteryl esters. The major cells that accumulate cholesterol in these lesions are macrophages which are derived from circulating monocytes that penetrate the endothelial barrier in response to inflammatory signals. Although the precise mechanism for subendothelial recruitment of monocytes and their subsequent accumulation of cholesterol is still speculative, it is generally believed that circulating cholesterol-rich lipoproteins, namely low-density lipoprotein (LDL), infiltrate the artery wall and become oxidized in the subendothelial space (Steinberg et al. 1989). These oxidized particles may be chemotactic and promote monocyte recruitment and their differentiation into macrophages. The cell membranes of these macrophages contain unique “scavenger” receptor proteins that bind oxidized LDL and allow the cells to engulf the bound particles and degrade their lipid and protein components (Brown and Goldstein 1983). The excess cholesterol liberated by this process is esterified by intracellular enzymes to form cholesterol ester lipid droplets.