Functional characteristics of the endothelium on the dynamics of experimental atherosclerosis

The aortic endothelium of rabbits, fed an atherogenic diet, has been studied by electron microscopy and by analysis of the distribution of intravenously injected, labeled, LDL and VLDL in plasma and aortic wall. It has been proposed that, in experimental hypercholesterolemia, when the receptor mechanism of lipoprotein uptake is saturated, a receptor-independent endocytosis plays the main role in the uptake of lipoproteins particles by endothelial cells. It has been established that, during the early stages of experimental hypercholesterolemia and atherosclerosis, there was an increase in the number of vesicles of 100-250 A in diameter, even up to 750 A, in the endothelial cells. Thus, it seems probable that there is transendothelial passage, not only of LDL, but also of particles like VLDL. Furthermore, the electron microscopy data have shown the possible formation of transedothelial canals by fusion of 3-4 vesicles. As hypercholesterolemia and atherosclerosis increase, the transport of lipoproteins occurs mostly through intercellular spaces and impaired endothelial regions. The intravenous administration to rabbits of LDL and VLDL, labeled with 14C-palmitic acid in their outer shell (phospholipids) and core (triglycerides + esters of cholesterol), has revealed a preferential penetration of small lipoprotein particles and of phospholipid-rich triglyceride-poor residues, both in normal and atherosclerotic aortas.