Fatty streak expansion and maturation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.

Abstract

This study focuses on the expansion and maturation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits between 2 and 6 months duration of hypercholesterolemia. In both groups of animals, the fatty streaks expanded due to: 1) the formation of multiple layers of a mixed population of macrophage-derived foam cells and lipid-containing smooth muscle cells, 2) the hypertrophy of the macrophage-derived foam cells, 3) the continued accumulation of extracellular matrix, 4) the insudation of plasma components. Immunocytochemical studies utilizing macrophage-specific and muscle-actin-specific monoclonal antibodies indicated that the expanding and mature fatty streaks in both the Watanabe and fat-fed rabbits were primarily composed of macrophage-derived foam cells. Hypertrophy of those foam cells situated immediately beneath the endothelium was associated with retraction of the endothelium and exposure of the intimal foam cells to the circulation. Endothelial retraction with exposure of intimal foam cells may facilitate entry of blood cells and lipoproteins into the lesions and formation of mural thrombi on the surfaces of the exposed cells. Biochemical analyses of the cholesterol content of the arteries indicated that both unesterified cholesterol and cholesteryl esters were deposited to a comparable degree in both the Watanabe and fat-fed rabbits. Thus, the absence of the low density lipoprotein receptor in Watanabe rabbits does not appear to directly influence the accumulation of cholesterol in the artery wall.