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 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.
Trigatti
B
B
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rayburn
H
H
Viñals
M
M
Braun
A
A
Miettinen
H
H
Penman
M
M
Hertz
M
M
Schrenzel
M
M
Amigo
L
L
Rigotti
A
A
Krieger
M
M
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D001646:Bile / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009928:Organ Specificity; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000502:physiology; D051116:Receptors, Scavenger; D012016:Reference Values; D051122:Scavenger Receptors, Class B; D012850:Sinus of Valsalva / Q000473:pathology
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008074:Lipoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol