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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-08, Vol.96 (16), p.9322-9327
• Main Authors: Trigatti, B, Rayburn, H, Vinals, M, Braun, A, Miettinen, H, Penman, M, Hertz, M, Schrenzel, M, Amigo, L, Rigotti, A, Krieger, M
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; aorta; Apolipoprotein A-I - blood; apolipoproteins; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Arteriosclerosis - genetics; Arteriosclerosis - pathology; Arteriosclerosis - physiopathology; Atherosclerosis; bile; Bile - physiology; Biological Sciences; blood chemistry; blood lipids; CD36 Antigens - genetics; CD36 Antigens - physiology; Cholesterol; Cholesterol - blood; Cholesterol - metabolism; Cholesterol, HDL - blood; Cholesterols; embryogenesis; Embryos; Female; Female animals; female fertility; Fertility; HDL lipoproteins; high density lipoprotein; Homozygote; Humans; knockout mutants; lesions; Lipids; Lipoproteins; Lipoproteins - blood; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; mutants; Oocytes; Organ Specificity; ovaries; pathophysiology; Proteins; receptors; Receptors, Immunologic; Receptors, Lipoprotein - physiology; Receptors, Scavenger; Reference Values; Scavenger Receptors, Class B; Sinus of Valsalva - pathology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.16.9322

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-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 early-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 SR-BI/apolipoprotein E double knockout mice relative to controls. If SR-BI has similar activities in humans, it may become an attractive target for therapeutic intervention in a variety of diseases.