The endothelium and lipoproteins: insights from recent cell biology and animal studies.

Both lipoproteins and the endothelium play critical roles in the initiation and progression of atherosclerosis. An understanding of the interactions between lipoproteins and the endothelium facilitates our understanding of atherogenesis and could suggest new therapeutic targets. Lipoproteins have important effects on endothelial cells. Atherogenic lipoproteins such as remnants, low-density lipoprotein (LDL), and oxidized LDL act on endothelial cells to cause upregulation of endothelial adhesion molecules and selectins, promotion of oxygen radicals, increased apoptosis, and reduced endothelium-dependent relaxation. Antiatherogenic lipoproteins such as HDL protect endothelial cells from oxidative stress and apoptosis and reduce adhesion molecule expression. Conversely, the endothelium has major effects on lipoprotein metabolism and function. Several lipases, including lipoprotein lipase, hepatic lipase, endothelial lipase, and secretory phospholipase A2, are bound to the endothelial cell matrix and have the ability to hydrolyze lipoprotein triglycerides and phospholipids. Furthermore, endothelial cells express a variety of lipoprotein receptors including the VLDL receptor, scavenger receptor A, SR-BI, CD36, and LOX-1, although little is known about their function on endothelial cells. Although a great deal is known about endothelial-lipoprotein interactions, more research is needed in this important area.