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Circulation, Vol 76, 508-514, Copyright © 1987 by American Heart Association

ARTICLES

Lipoproteins and the pathogenesis of atherosclerosis

D Steinberg

It is now clear that hypercholesterolemia can, in some instances, be a necessary and sufficient cause of premature atherosclerosis. This has been best established in patients with familial hypercholesterolemia, a deficiency of the low-density lipoprotein receptor. Although hypercholesterolemia is not the only cause of atherosclerosis, a large body of evidence has identified it as a determining cause in many cases. This article reviews current hypotheses regarding the mechanisms by which hypercholesterolemia accelerates atherogenesis. The role of the foam cell is discussed in detail because it is a characteristic feature of the earliest lesion, the so-called fatty streak. Once thought to derive exclusively from smooth muscle cells, the foam cell is now known to originate in large part from monocytes that enter the artery wall and alter their properties to become tissue macrophages. Recent studies of the biology of the macrophage-derived foam cell are providing new insights into the mechanisms by which it enters the arterial wall and interacts with various classes of native and modified lipoproteins. As our understanding of the biology of the foam cell and its precursors grows, it may become possible to intervene and slow the progress of atherosclerosis by new modalities that might act synergistically with measures to control plasma cholesterol levels.

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