The role of scavenger receptor class B type I (SR-BI) in lipid trafficking - Defining the rules for lipid traders

The scavenger receptor class B type I (SR-BI) is a 509-amino acid, 82 kDa glycoprotein, with two cytoplasmic C- and N-terminal domains separated by a large extracellular domain. The aim of this review is to define the role of SR-BI as a lipoprotein receptor responsible for selective uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) and low density lipoprotein (LDL) and free cholesterol (FC) efflux to lipoprotein acceptors. These activities depend on lipoprotein binding to its extracellular domain and subsequent lipid exchange at the plasma membrane. CE selective uptake supplies cholesterol to liver and steroidogenic tissues, for biliary cholesterol secretion and steroid hormone synthesis. Genetically modified mice have confirmed SR-BI's major role in tissue cholesterol uptake and in reverse cholesterol transport, i.e. cholesterol turnover. Accordingly, cellular cholesterol level, estrogens and trophic hormones regulate SR-BI expression by both transcriptional and post-transcriptional mechanisms. Importantly, mouse SR-BI overexpression has both corrective and preventive effects on atherosclerosis. Human SR-BI has very similar tissue distribution, binding properties and lipid transfer activities compared to rodent SR-BI. However, human plasma has most of its cholesterol in LDL. Thus, there is considerable interest to develop anti-atherogenic strategies involving human SR-BI-mediated increases in reverse cholesterol transport through HDL and/or LDL. (C) 2003 Elsevier Science Ltd. All rights reserved.