Novel Functions of Endothelial Scavenger Receptor Class B Type I

Abstract

Scavenger receptor class B type I (SR-BI) serves a key role in the reverse cholesterol transport in the liver as the high-affinity receptor for HDL. SR-BI is abundantly expressed in endothelium, and earlier works indicate that the receptor mediates anti-atherogenic actions of HDL. However, more recent studies uncovered novel functions of endothelial SR-BI as a lipoprotein transporter, which regulates transcellular transport process of both LDL and HDL. This brief review focuses on the unique functions of endothelial SR-BI and how they influence atherogenesis. Earlier studies indicate that SR-BI facilitates anti-atherogenic actions of HDL through modulation of intracellular signaling to stimulate endothelial nitric oxide synthase. In vivo studies in global SR-BI knockout mice also showed a strong atheroprotective role of the receptor; however, a contribution of endothelial SR-BI to atherosclerosis process in vivo has not been fully appreciated. Recent studies using cultured endothelial cells and in mice with endothelial-specific deletion of the receptor revealed previously unappreciated pro-atherogenic actions of SR-BI, which relates to its ability to deliver LDL into arteries. On the other hand, SR-BI has also been implicated in transport of HDL to the sub-intimal space as a part of reverse cholesterol transport. SR-BI mediates internalization and transcellular transport of both HDL and LDL, and the cellular and molecular mechanism of the process has just begun to emerge. Harnessing these dual transport functions of the endothelial SR-BI may provide a novel, effective intervention to atherosclerosis.