Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam cells via PPARgamma-LXRalpha-ABCA1-dependent pathway associated with apoE

Cell Biochem Funct. Jan-Feb 2007;25(1):33-44. doi: 10.1002/cbf.1374.

Abstract

Formation of macrophage-derived foam cells is a hallmark in earlier stages of atherosclerosis (AS). Increased cholesterol efflux from macrophage foam cells promote atherosclerotic regression. In the present study, lysophosphatidylcholine (LPC) promoting cholesterol efflux from macrophage foam cells was observed, and the mechanism underlying the action was investigated. Macrophage foam cells from mice were incubated with different concentrations of LPC (10, 20, 40, 80 microM), and the free cholesterol in medium increased but total intracellular cholesterol decreased. At the same time, the expression of PPARgamma, LXRalpha, ABCA1 was enhanced in a dose-dependent manner. The treatment of macrophage foam cells with 40 microM LPC for 12, 24 and 48 h promoted cellular cholesterol efflux in a time-dependent manner, meanwhile expression of PPARgamma, LXRalpha, ABCA1 was also raised respectively. Addition of different specific inhibitors of PPARgamma (GW9662), LXRalpha (GGPP), ABCA1 (DIDS) to the foam cells significantly suppressed LPC-induced cholesterol efflux. Also treatment with specific inhibitors of PPARgamma or LXRalpha decreased ABCA1 mRNA and protein expressions. LPC (40 microM)-induced cholesterol efflux was significantly lower in macrophage foam cells from apoE deficient mice than from normal C57BL/6J mice. In contrast, 10 microg apoAI-induced cholesterol efflux from foam cells remained in apoE deficient mice. The present results indicate that LPC promotes cholesterol efflux from macrophage foam cells via a PPARgamma-LXRalpha-ABCA1-dependent pathway. Furthermore, apoE may be involved in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Cells, Cultured
  • Cholesterol / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Liver X Receptors
  • Lysophosphatidylcholines / pharmacology*
  • Mice
  • Mice, Knockout
  • Orphan Nuclear Receptors
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • DNA-Binding Proteins
  • Liver X Receptors
  • Lysophosphatidylcholines
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • PPAR gamma
  • Receptors, Cytoplasmic and Nuclear
  • Cholesterol