Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis

MS Brown, JL Goldstein - Annual review of biochemistry, 1983 - annualreviews.org
MS Brown, JL Goldstein
Annual review of biochemistry, 1983annualreviews.org
Atherosclerotic plaques are filled with scavenger cells that have ingested large amounts of
cholesterol and have become so stuffed with cholesteryl ester that they are converted into
foam cells (1, 2). Most of these foam cells arise either from resident macrophages of the
artery wall or from blood monocytes that enter the wall at sites of endothelial damage.
Macrophages ingest and degrade cholesterol-carrying plasma lipoproteins that have leaked
through damaged endothelium and penetrated into the tissue of the wall. When …
Atherosclerotic plaques are filled with scavenger cells that have ingested large amounts of cholesterol and have become so stuffed with cholesteryl ester that they are converted into foam cells (1, 2). Most of these foam cells arise either from resident macrophages of the artery wall or from blood monocytes that enter the wall at sites of endothelial damage. Macrophages ingest and degrade cholesterol-carrying plasma lipoproteins that have leaked through damaged endothelium and penetrated into the tissue of the wall. When macrophages take up more lipoprotein cholesterol than they can excrete, the cholesterol is stored in the cytoplasm in the form of cho lesteryl ester droplets. These droplets give the cytoplasm a foamy appear ance in the electron microscope, thus accounting for the term foam cell. The atherosclerotic plaque is a complicated structure. In addition to cholesterol-filled macrophages, the structure contains large numbers of proliferating smooth muscle cells and a large amount of extracellular mate rial that includes sulfated glycosaminoglycans, collagen, fibrin, and choles terol (3). Some of the smooth muscle cells contain cholesteryl ester droplets that resemble those of macrophage foam cells. In order to unravel such a complicated structure, in recent years scientists have begun to study the specialized properties of each of the cell types that comprise the lesion. For example, endothelial cells and smooth muscle cells were propagated in vitro, and their analyses identified several distinctive properties that might contribute to the initiation of atherosclerosis (reviewed in 3). The macrophage, too, has come under study. Extensive investigations over the past five years disclosed that macrophages, isolated from the peritoneal cavity of mice and from the blood of man, possess mechanisms that allow them to take up and digest cholesterol-containing lipoproteins, to store the sterol, and to excrete it in large amounts when conditions permit (4-8). These mechanisms differ from those in other cell types, such as cultured fibroblasts and smooth muscle cells. Awareness of these special mechanisms for lipoprotein uptake made possible the conversion of macro phages into foam cells in vitro (4, 8). These studies shed new light on the possible mechanism for foam cell formation in vivo. The uptake of lipoprotein-bound cholesterol in macrophages occurs through the process of receptor-mediated endocytosis (4-7). The initial event is the binding of the lipoprotein to a cell surface receptor. Although macrophages express few receptors for normal plasma lipoproteins, they exhibit abundant receptors for lipoproteins that have been altered by chemi cal derivitization (4) or by complexing with other molecules (5, 7). In addition, macrophages have receptors for at least one type of abnormal lipoprotein that accumulates spontaneously in plasma in hyperlipidemic states (6).
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