Lipids and the Endothelium: Bidirectional Interactions

The endothelium is often viewed solely as the barrier that prevents the penetration of circulating lipoproteins into the arterial wall. However, recent research has demonstrated that the endothelium has an important part in regulating circulating fatty acids and lipoproteins, and is in turn affected by these lipids/lipoproteins in ways that appear to have important repercussions for atherosclerosis. Thus, a number of potentially toxic lipids are produced during lipolysis of lipoproteins at the endothelial cell surface. Catabolism of triglyceride-rich lipoproteins creates free fatty acids that are readily taken up by endothelial cells, and, likely through the action of acyl-CoA synthetases, exacerbate inflammatory processes. In this article, we review how the endothelium participates in lipoprotein metabolism, how lipids alter endothelial functions, and how lipids are internalized, processed, and transported into the subendothelial space. Finally, we address the many endothelial changes that might promote atherogenesis, especially in the setting of diabetes.