Endothelial proliferation and atherogenesis in rabbits with moderate hypercholesterolemia

The formation and growth of atherosclerotic lesions in experimental hypercholesterolemia has been attributed to endothelial injury. Many injured endothelial cells have been observed in the periphery of the lesions, but few in the central parts. In the present study, we have investigated the distribution of endothelial cells, leucocytes, and smooth muscle cells on the surface of the lesions, as well as the regeneration of the surface cell layer, on dietary induced experimental atherosclerotic lesions. In central areas of the lesions, flat cells with Weibel-Palade bodies and intercellular junctions characteristic of endothelium, were observed on the surface. In peripheral areas of the lesions, surface cells were more bulging and contained many free ribosomes and short cisternae of endoplasmic reticulum, suggesting that these cells were more primitive. Weibel-Palade bodies and typical intercellular junctions suggested that many of the cells should be regarded as endothelial cells. ANAE- positive monocytes were also frequent in these areas. The incorporation of 3H-thymidine was considerably larger over the lesions than in the surrounding normal tissue, suggesting a regeneration of the endothelial cell layer from cells on the lesions. Still regression does not occur after re-endothelialization in dietary induced atherosclerosis. This contrasts with the development of lesions induced by mechanical injury, and may be of importance for understanding the role of hypercholesterolemia in atherogenesis.