Genetic studies in mice and humans reveal new physiological roles for the high-density lipoprotein receptor scavenger receptor class B type I.

Scavenger receptor class B type I (BI) is primarily known for its role in the selective uptake of cholesteryl esters from HDL, the final step in reverse cholesterol transport. Here, we will discuss findings that highlight the recently established novel link between scavenger receptor BI and adrenal and platelet function. Human heterozygote carriers of a functional P297S mutation in the scavenger receptor BI gene show an attenuated adrenal glucocorticoid output and an altered platelet function. Scavenger receptor BI knockout mice lack adrenal cholesteryl ester stores and suffer from primary adrenal glucocorticoid insufficiency, indicating that adrenal HDL cholesteryl ester uptake by scavenger receptor BI is needed for generating the cholesterol pool used for steroidogenesis. Scavenger receptor BI knockout mice exhibit thrombocytopenia, an impaired platelet aggregation response, and higher susceptibility for arterial thrombosis. Bone marrow-specific deletion of scavenger receptor BI in mice indicates that scavenger receptor BI indirectly modulates platelet function through regulation of plasma cholesterol levels. Scavenger receptor BI is not merely a crucial mediator of reverse cholesterol transport, but rather acts as a multipurpose player in cholesterol and steroid metabolism. Further understanding of the contribution of scavenger receptor BI's roles in adrenal steroidogenesis and platelet function to the pathogenesis of atherosclerosis and atherothrombosis will hopefully show its potential as a therapeutic target for cardiovascular benefit.