Abstract-High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. In this process, a scavenger receptor of the B class (SR-BI)/human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from high-density lipoprotein. 1,2 In this process, HDL particles shuttle cholesterol from extrahepatic tissues to the liver for further metabolism and excretion. 1 Enhanced reverse cholesterol transport lowers total body cholesterol and thereby reduces the risk of developing coronary artery disease. Thus, the plasma concentration of HDL is inversely related to the incidence of coronary artery disease. 3 The mouse scavenger receptor class BI (SR-BI) mediates selective uptake of HDL cholesterol ester into transfected Chinese hamster ovary cells. This finding provides an important link between a specific cell surface receptor and a pathway for the uptake of HDL. 4 Our previous reports show that human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1), like mouse SR-BI, functions as a receptor for HDL. 5,6 However, the mechanisms by which HDL is atheroprotective are complex and not well understood.Endothelial dysfunction plays a pivotal role in the initiation and progression of atherosclerosis. In fact, the vascular endothelium modulates the vessel tone by releasing both relaxing and contractile factors, 7 regulates the adherence of mononuclear cells to its surface and the vascular permeability, 8,9 and produces substances involved in the regulation of hemostasis and tissue proliferation. 10 The release of NO by endothelial NO synthase (eNOS) is important in the regulation of cardiovascular homeostasis. Recent reports indicated that SR-BI and eNOS are colocalized in vascular endothelial cells. Thus, HDL activates eNOS via SR-BI, and the resulting