STUDIES ON THE PATHOGENESIS OF ATHEROSCLEROSIS .1. ADHESION AND EMIGRATION OF MONONUCLEAR-CELLS IN THE AORTA OF HYPERCHOLESTEROLEMIC RATS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 113  (3) , 341-358
Abstract
In rats with diet-induced hypercholesterolemia, 2 concomitant changes began to occur within 1 wk and persisted for 1 yr: an increase in total plasma cholesterol and an increase in the number of mononuclear cells adhering to the aortic intima (up to values 50 times normal). Adherent cells were .apprx. 90% monocytes and .apprx. 10% lymphocytes. Adhesion was focal, with some preference for ostia of aortic branches; it was followed by migration into the subendothelial space. The subendothelial monocytes/macrophages progressively became foam cells, thus giving rise to microscopic fatty streaks. Ultimately, typical atherosclerotic plaques were formed. Four possible mechanisms of increased cell adhesion are suggested. Endothelial changes were mild; myelin figures arising from the endothelial surface were ween by EM. Endothelial denudation was never observed, neither in light microscopic preparations stained with AgNO3 nor by ultrastructure. Platelet participation was minimal. Evidently, in this model atherosclerotic plaques are initiated by mononuclear cell adhesion and emigration; endothelial denudation is not a necessary step in their pathogenesis.