Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells

Acta Pharmacol Sin. 2010 Oct;31(10):1343-9. doi: 10.1038/aps.2010.166. Epub 2010 Sep 27.

Abstract

Aim: 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.

Conclusion: Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / metabolism*
  • Benzamides / pharmacology*
  • Biological Transport
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholesterol / metabolism
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Lipoprotein Lipase Activators / pharmacology*
  • Liver X Receptors
  • Organophosphorus Compounds / pharmacology*
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Benzamides
  • Lipoprotein Lipase Activators
  • Liver X Receptors
  • NR1H3 protein, human
  • Organophosphorus Compounds
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
  • Cholesterol