Contribution of the endothelium to intimal thickening in normocholesterolemic and hypercholesterolemic rabbits.
Endothelial cell injury is considered to be a primary event in the pathogenesis of atherosclerosis. In this study, we investigated the aortic intimal lesion after balloon catheterization in hypercholesterolemic and normocholesterolemic rabbits with or without probucol, an antioxidant. After deendothelialization, the rabbits were divided into four groups: 1) a control group fed a standard diet; 2) a probucol-treated group; 3) a cholesterol-fed group; and 4) a group fed a mixed cholesterol and probucol diet. Four animals from each group were killed at 2, 4, and 8 weeks after deendothelialization. The aortic segments of nonendothelialized areas, borderline areas, and uninjured areas were histologically and immunohistochemically examined. Deendothelialized areas showed various degrees of intimal thickening, which was mainly composed of smooth muscle cells in rabbits from groups 1 and 2. The intimal thickness of group 3 was significantly larger than that of other groups in any area examined. The intimal thickness of group 4 was less than that of group 3 despite the hypercholesterolemic state in the former group. The intima of borderline areas was generally thicker than that of nonendothelialized areas. Although the borderline lesions of groups 3 and 4 contained numerous macrophages, the number of macrophages was lower in the nonendothelialized compared with the reendothelized lesion. These data indicate that endothelial cell injuries can cause intimal thickening. The regenerated endothelial covering is favorable for monocyte migration and attachment. This process, together with the proliferation of smooth muscle cells, greatly contributes to the progression of atherosclerosis, which appears to involve lipid oxidation. Probucol prevented intimal thickening to a certain degree in this experiment in the normocholesterolemic as well as the hypercholesterolemic state.
- Copyright © 1992 by American Heart Association