Macrophages, Endothelial Cells, and Lipoprotein Oxidation in the Pathogenesis of Atherosclerosis*

Toxicologic Pathology - Tập 18 Số 4a - Trang 560-571 - 1990
Michael E. Rosenfeld1, Wulf Palinski1, Seppo Ylä‐Herttuala1, T E Carew1
1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093

Tóm tắt

One of the earliest phenomena in the atherogenic process in cholesterol-fed rabbits appears to be the trapping of low density lipoproteins (LDL) at lesion-prone sites in the aorta. The resulting increase in residence time may facilitate oxidation of the lipoproteins, which, in turn, may be a chemotactic signal for monocytes to enter the intima. Oxidized lipoproteins may also be the major source of the cholesterol that the cells accumulate during their transformation into macrophage-derived foam cells (MFC). Adherent monocytes appear to cluster over small groups of subendothelial foam cells, perhaps in response to the enhanced expression of specific adhesion molecules on the surface of endothelial cells and/or monocytes following activation by oxidized lipoproteins. Lipoproteins oxidized by MFC may also injure endothelial cells causing them to retract or rupture. The resulting exposure of the MFC facilitates the formation of mural thrombi. MFC contain oxidation-specific lipid-protein adducts and specifically express the mRNA for 15-lipoxygenase, an enzyme potentially involved in lipoprotein oxidation. MFC isolated from atherosclerotic lesions and containing up to 600 μg cholesterol/mg protein are still capable of binding and degrading modified lipoproteins and affecting the oxidation of LDL.

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Toxicologic Pathology

Tập 18 Số 4a

560-571

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