SR-BI inhibits ABCG1-stimulated net cholesterol efflux from cells to plasma HDL.
This study compares the roles of ABCG1 and scavenger receptor class B type I (SR-BI) singly or together in promoting net cellular cholesterol efflux to plasma HDL containing active LCAT. In transfected cells, SR-BI promoted free cholesterol efflux to HDL, but this was offset by an increased uptake of HDL cholesteryl ester (CE) into cells, resulting in no net efflux. Coexpression of SR-BI with ABCG1 inhibited the ABCG1-mediated net cholesterol efflux to HDL, apparently by promoting the reuptake of CE from medium. However, ABCG1-mediated cholesterol efflux was not altered in cholesterol-loaded, SR-BI-deficient (SR-BI(-/-)) macrophages. Briefly cultured macrophages collected from SR-BI(-/-) mice loaded with acetylated LDL in the peritoneal cavity did exhibit reduced efflux to HDL. However, this was attributable to reduced expression of ABCG1 and ABCA1, likely reflecting increased macrophage cholesterol efflux to apolipoprotein E-enriched HDL during loading in SR-BI(-/-) mice. In conclusion, cellular SR-BI does not promote net cholesterol efflux from cells to plasma HDL containing active LCAT as a result of the reuptake of HDL-CE into cells. Previous findings of increased atherosclerosis in mice transplanted with SR-BI(-/-) bone marrow probably cannot be explained by a defect in macrophage cholesterol efflux.
Yvan-Charvet
Laurent
L
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA. ly2159@columbia.edu
Pagler
Tamara A
TA
Wang
Nan
N
Senokuchi
Takafumi
T
Brundert
May
M
Li
Hongna
H
Rinninger
Franz
F
Tall
Alan R
AR
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D000071518:Liver X Receptors; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D057093:Orphan Nuclear Receptors; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D014162:Transfection
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; C059714:HDL cholesteryl ester; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase