The endothelium, triglyceride-rich lipoproteins, and atherosclerosis: insights from cell biology and lipid metabolism.

Endothelial cells in culture retain many of the functional properties of the endothelium in vivo. At high cell density, they become contact-inhibited. Endothelial cells, like vascular smooth muscle cells and fibroblasts, express binding sites for low density lipoprotein when depleted of sterol. In contact-inhibited endothelial cells (but not actively growing cells), a block to internalization is evident, so that the cells bind but do not interiorize low density lipoprotein. Lipoprotein sterol does not enter the cell or regulate endogenous sterol synthesis. On the other hand, both contact-inhibited and actively growing endothelial cells express a separate receptor for triglyceride-rich lipoproteins. Cholesterol in these lipoproteins, unlike that in LDL, effectively regulates sterol synthesis in contact-inhibited endothelial cells and also mediates the accumulation of cholesterol in these cells. These findings are related to current concepts of atherogenesis. Receptors for triglyceride-rich lipoproteins may promote cellular sterol accumulation, release of contact inhibition in the surrounding endothelial cells, and exposure of the underlying vascular smooth muscle cells to plasma concentrations of both triglyceride-rich lipoproteins and LDL.