The Role of Macrophage Scavenger Receptors in Atherogenesis

Abstract

The development of atherosclerosis is induced by deposition of low density lipoproteins (LDL) in the arterial walls and followed by migration of monocytes from peripheral blood into the arterial walls, uptake of oxidized LDL (OxLDL) by macrophages, accumulation of cholesterol ester in macrophages, their transformation into foam cells, and numerical increment of foam cells in the atherosclerotic lesions. In the fatty streak lesions, the number of macrophage-derived foam cells increases in the arterial intima and a part of macrophage-derived foam cells proliferate in loco. During the processes of foam cell transformation, OxLDL is actively ingested by macrophages, is digested and degraded into amino acids and free cholesterol within lysosomes. Free cholesterol is released from the lysosomes into the cytosol, excess of cholesterol ester is accumulated in membrane-free lipid droplets by catalyzing with acyl coenzyme A:holesterol acyItransferase-1 (ACAT-1), and intracellular accumulation of lipid droplets changes macrophages into foam cells. In the atherosclerotic plaques, the number of macrophage- derived foam cells increases more than in the fatty streak lesions, and besides the macrophage derived foam cells, smooth muscle cells migrate from the subintimal layer and media of arteries. accumulate lipid droplets in the cytoplasm, and transform into foam cells. In the center of the plaques, necrotic lipid cores are formed. In the complicated lesions, the central lipid cores become enlarged with increased numbers of foam cells of both macrophage and smooth muscle cell origins, accompanied by arterial surface ulceration, thrombosis, and calcification.