Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the l iver and steroidogenic tissues. As a consequence, SR-BI can influence plasm a HDL cholesterol levels, HDL structure, biliary cholesterol concentrations , and the uptake, storage, and utilization of cholesterol by steroid hormon e-producing cells. Here we used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility. We also used SR-BI/apolipoprotein E double homozygous knockout mice to show that SR-BI can protect against e arly-onset atherosclerosis. Although the mechanisms underlying the effects of SR-BI loss on reproduction and atherosclerosis have not been established , potential causes include changes in (i) plasma lipoprotein levels and/or structure, (ii) cholesterol flux into or out of peripheral tissues (ovary, aortic wall), and (iii) reverse cholesterol transport, as indicated by the significant reduction of gallbladder bile cholesterol levels in SR-BI and S R-BI/apolipoprotein E double knockout mice relative to controls. If SR-BI h as similar activities in humans, it may become an attractive target for the rapeutic intervention in a variety of diseases.