Aspirin increases apolipoprotein-A-I-mediated cholesterol efflux via enhancing expression of ATP-binding cassette transporter A1

Pharmacology. 2010;86(5-6):320-6. doi: 10.1159/000321727. Epub 2010 Nov 19.

Abstract

Background: The efflux of cellular cholesterol mediated by apolipoprotein (apo)A-I and ATP-binding cassette transporter A1 (ABCA1) is a major pathway of reverse cholesterol transport. We investigated the effect of aspirin on this process.

Methods: The expression levels of ABCA1 in RAW264.7 cells were determined using reverse transcription polymerase chain reaction and Western blot analysis. ³H-cholesterol efflux was measured by scintillation counting.

Results: 0.5 mmol/l aspirin increased apoA-I-mediated cholesterol efflux and increased the expression of ABCA1. By increasing the dose of aspirin higher than 0.5 mmol/l, ABCA1 expression and function were significantly decreased. In cells transfected with a specific peroxisome proliferator-activated receptor (PPAR)-α small interfering RNA, the induction of ABCA1 expression and apoA-I-mediated ³H-cholesterol efflux by aspirin were substantially suppressed.

Conclusions: The data demonstrate that low-dose aspirin increases ABCA1 expression via a PPAR-α-dependent mechanism and increases apoA-I-mediated cholesterol efflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Apolipoprotein A-I / metabolism*
  • Aspirin / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Gene Expression Regulation / drug effects
  • Mice
  • PPAR alpha / metabolism
  • Platelet Aggregation Inhibitors / pharmacology
  • RNA, Small Interfering / administration & dosage
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scintillation Counting
  • Transfection

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I
  • PPAR alpha
  • Platelet Aggregation Inhibitors
  • RNA, Small Interfering
  • Cholesterol
  • Aspirin