Statins downregulate ATP-binding-cassette transporter A1 gene expression in macrophages

Biochem Biophys Res Commun. 2004 Apr 9;316(3):790-4. doi: 10.1016/j.bbrc.2004.02.121.

Abstract

The ATP-binding-cassette transporter A1 (ABCA1) plays an essential role in cellular cholesterol efflux and helps prevent macrophages from becoming foam cells. The statins are widely used as cholesterol-lowering agents and have other anti-atherogenic actions. We tested the effects of four different statins (fluvastatin, atorvastatin, simvastatin, and lovastatin) on ABCA1 expression in macrophages in vitro. The statins suppressed ABCA1 mRNA expression in RAW246.7 and THP-1 macrophage cell lines and in mouse peritoneal macrophages. The effect was time- and dose-dependent and was abolished by the addition of the post-reductase product, mevalonate. These findings imply that there is a possible modulation of the well-known beneficial effects of the statins on the reverse cholesterol transport pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / physiology*
  • Animals
  • Atorvastatin
  • Biological Transport
  • Blotting, Northern
  • Cell Line
  • Cholesterol / metabolism
  • Dose-Response Relationship, Drug
  • Fatty Acids, Monounsaturated / pharmacology
  • Fluvastatin
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Indoles / pharmacology
  • Lovastatin / pharmacology
  • Luciferases / metabolism
  • Macrophages / metabolism
  • Mice
  • Oxygen / metabolism
  • Promoter Regions, Genetic
  • Pyrroles / pharmacology
  • RNA, Messenger / metabolism
  • Simvastatin / pharmacology
  • Swiss 3T3 Cells
  • Time Factors
  • Transcription, Genetic

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Fatty Acids, Monounsaturated
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Pyrroles
  • RNA, Messenger
  • Fluvastatin
  • Cholesterol
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • Luciferases
  • Oxygen