Abstract-Elevated plasma levels of HDL cholesterol or apolipoprotein A-I, the major protein moiety of HDL particles, are protective against coronary artery disease. HDL particles remove cholesterol from peripheral cells and transfer it to the liver for bile acid synthesis. The interaction between lipoproteins is not mediated through simple contact between 2 phospholipid membranes but involves specific protein-receptor interactions, charged phospholipid-phospholipid contact, and activation of cellular signaling pathways. These lead to regulation of genes or the modification of proteins involved in vasomotor function, platelet activation, thrombosis and thrombolysis, cell adhesion, apoptosis and cell proliferation, and cellular cholesterol homeostasis. Key Words: endothelium Ⅲ lipoproteins Ⅲ atherosclerosis V ascular endothelial cells constitute a structurally simple but functionally sophisticated organ that regulates biological processes as diverse as hemostasis, fibrinolysis, inflammation, blood pressure, lipoprotein metabolism, and angiogenesis. Although the endothelium consists of a monolayer of cells, it has an important aggregate surface area and mass. Alterations in one or more of the physiological roles of vascular endothelial cells constitutes endothelial dysfunction. In clinical practice, endothelial function is measured indirectly, by examining the ability of an artery to vasodilate in response to a stimulus that causes NO release in a healthy blood vessel. Techniques for measurement are described elsewhere. 1 Endothelial dysfunction is seen in a variety of metabolic disorders, including diabetes and dyslipoproteinemia, and in patients with established atherosclerosis.Endothelial cells are continuously exposed to blood-borne substances that exert multiple regulatory functions on endothelial cells in an endocrine, paracrine, and autocrine fashion. Plasma lipoproteins have been shown to alter endothelial function in vivo in both the long and short term. Patients with elevated LDLs and triglyceride-rich lipoproteins have abnormal vasodilatory function in response to flow-mediated dilatation and are associated with the development of atherosclerosis. HDLs, conversely, are antiatherogenic and appear to modulate endothelial function in an beneficial fashion. 2 The present review will focus on the effects of HDL on endothelial cells and propose mechanisms by which HDL protects against atherosclerosis. High-Density LipoproteinsHDLs are a heterogeneous group of small, dense lipoproteins isolated from human plasma at a density of 1.063 to 1.125 g/mL. The majority of circulating HDL particles are spherical, with a diameter of 7 to 14 nm. Proteins represent Ϸ50% of HDL mass; the remainder is composed of lipids. The major proteins associated with HDL are apolipoprotein (apo) A-I (70%) and apoA-II (20%). Several other proteins, including apoA-IV, apoE, clusterin (apoJ), paraoxanase, haptoglobin, ␣ 2 -macroglobulin, and lecithin cholesterol acyltransferase, are also associated with HDL and impart significant physiolog...

Background— Of the cells that compose the atherosclerotic plaque, vascular endothelial cells are the most resistant to cholesterol accumulation. Cholesterol efflux pathways may play an important role in endothelial cholesterol homeostasis. Methods and Results— We examined the global genetic response of endothelial cells to cholesterol and in particular the contribution of the cholesterol efflux proteins ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor B-I (SR-BI) to endothelial cell cholesterol efflux. The ABCG1 gene is induced in endothelial cells by cholesterol, whereas ABCA1 is not. Using specific chemical inhibitors of ABC transporters and SR-BI, we have shown that neither ABC transporters nor SR-BI is required for apolipoprotein A-1–mediated endothelial cholesterol efflux. Conclusions— Endothelial cells may use nontraditional pathways for cholesterol efflux.