A Putative Mechanism for the Conversion of Aortic Smooth Muscle Cells into Foam Cells that Bypasses the Autoregulatory LDL Receptor-Mediated Process

Abstract

The most prominent feature of atheromatosis is deposition of cholesteryl ester (CE) in the arterial wall. The origin of the arterial CE are plasma lipoproteins, yet the mechanisms involved in the intracellular accumulation of this CE have not been clarified completely. Smooth muscle cells, which constitute the main cellular population of normal aorta, become loaded with esterified cholesterol during development of atheroma and change into foam cells. Very often it is difficult to identify the foam cells as a SMC but careful morphological examination can still be quite helpful as demonstrated in Figs. 1 and 2 which are sections of rabbit aorta after 2 months of 1% cholesterol feeding. To reproduce such changes in culture, smooth muscle cells were exposed to LDL, the accepted donor of cellular CE. However, since LDL is taken up by SMC through a receptor-mediated process (1), accumulation of CE is prevented by autoregulation. The same is true also for β–VLDL (2) formed during feeding of high cholesterol diets. It is possible to induce CE accumulation in SMC by disruption of the autoregulation mechanism as was achieved by exposure of SMC to high concentrations of LDL in the presence of chloroquine, an inhibitor of lysosomal cholesteryl ester hydrolase (3). CE accumulation in SMC in culture will occur also when the donor LDL has been cationized and therefore taken up by a nonreceptor-mediated uptake (4). Since neither chloroquine nor cationized LDL are present in the atheromatous aorta in situ, the question still remains how does enrichment of smooth muscle cells with CE, and their conversion into foam cells occur during development of an atheroma.