Scavenger receptor class B type I-mediated protection against atherosclerosis in LDL receptor-negative mice involves its expression in bone marrow-derived cells.
OBJECTIVE
Scavenger receptor class B type I (SR-BI) is a cell-surface HDL receptor that is implicated in reverse cholesterol transport and protection against atherosclerosis. We have previously demonstrated that SR-BI/apolipoprotein E double-knockout mice develop severe occlusive coronary artery disease and myocardial infarction and die at approximately 6 weeks of age. To determine if this is a general effect of a lack of SR-BI, we generated mice deficient in both SR-BI and the LDL receptor.


RESULTS
Complete ablation of SR-BI expression in LDL receptor knockout mice resulted in increased plasma cholesterol associated with HDL particles of abnormally large size and a 6-fold increase in diet-induced aortic atherosclerosis but no macroscopic evidence of early-onset coronary artery disease, cardiac pathology, or early death. Furthermore, selective elimination of SR-BI expression in bone marrow-derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant alterations in the distributions of plasma lipoprotein cholesterol.


CONCLUSIONS
SR-BI expression protects against atherosclerosis in LDL receptor-deficient as well as apolipoprotein E-deficient mice, and its expression in bone marrow-derived cells contributes to this protection.
Covey
Scott D
SD
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Krieger
Monty
M
Wang
Wei
W
Penman
Marsha
M
Trigatti
Bernardo L
BL
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D004036:Diet, Atherogenic; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011971:Receptors, Immunologic; D011973:Receptors, LDL / Q000172:deficiency*; D018110:Receptors, Lipoprotein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B