ORIGIN OF LIPID AND CHOLESTEROL IN EXPERIMENTAL THROMBOATHEROSCLEROSIS*

Open Access
Publisher Website
Google Scholar
Abstract
Thrombo-atherosclerotic plaques were induced in the aortas of 115 rabbits by single intravascular thrombi and cholesterol-oil feeding according to published techniques. The pathogenesis of the accumulation of lipid in these plaques was studied as follows 1) by histological examination of the early development of a plaque, 2) by growth of the excised plaque material in recipient rabbits while totally enclosed in filter material having 3 [mu] pores, hence under avascular conditions in the absence of new capillaries and arterioles, 3) by determination of in vitro incorporation of acetate-1-C14 by excised plaque material, 4) by determination of the in vivo uptake of orally administered cholesterol-4-C14, and 5) by observation of the permeability of newly formed capillaries attending intimal hyperplasia to Evans blue, Trypan blue, Thorotrast and 3 [mu] iron particles, and by observation of the localization of these materials in and about the plaque. Early plaques showed stained lipid and mucopolysaccharide in the basal layer of the newly developing hyper-plastic intima and the inner third of the subjacent media, the same areas in which large new capillaries were observed most frequently. Stained lipid was not seen in the superficial intimal areas adjacent to the luminal blood. Intimal tissue grown under avascular conditions contained no capillaries, stainable lipid, or excess accumulation of cholesterol; similarly grown tissue, allowed access to capillaries, was richly vascular, sudanophilic and showed a fourfold increase in cholesterol. The hyperplastic intimal tissue of a newly developing plaque incorporated acetate-1-C14 into cholesterol at the same rate as normal, uninvolved aorta; however, this hyperplastic tissue in vivo took up far more cholesterol-4-Cl4 than did normal aorta. The new blood vessels in early plaques were much more permeable to dyes and 3[mu] particles than were older blood vessels. Phagocytized particles were seen both at the base of plaques and also superficially. It is concluded that the early thromboatherosclerotic plaque developing in the hypercholesteremic rabbit accumulates lipid coming from excessively permeable new capillaries, almost certainly of adventitial origin.