Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.
OBJECTIVE
To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis.


METHODS
Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays.


RESULTS
Ibrolipim 5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim.


CONCLUSIONS
Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.
Chen
Si-guo
SG
Institute of Cardiovascular Research, Life Science Research Center, University of South China, Hengyang, China.
Xiao
Ji
J
Liu
Xie-hong
XH
Liu
Mei-mei
MM
Mo
Zhong-cheng
ZC
Yin
Kai
K
Zhao
Guo-jun
GJ
Jiang
Jin
J
Cui
Li-bao
LB
Tan
Chun-zhi
CZ
Yin
Wei-dong
WD
Tang
Chao-ke
CK
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D058867:Lipoprotein Lipase Activators / Q000494:pharmacology*; D000071518:Liver X Receptors; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001549:Benzamides; D058867:Lipoprotein Lipase Activators; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D009943:Organophosphorus Compounds; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D002784:Cholesterol