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

Hirohito Sone, Hitoshi Shimano*, Miao Shu, Masanori Nakakuki, Akimitsu Takahashi, Masakazu Sakai, Yuichiro Sakamoto, Tomotaka Yokoo, Ken Matsuzaka, Hiroaki Okazaki, Yoshimi Nakagawa, Kaoruko Tada Iida, Hiroaki Suzuki, Hideo Toyoshima, Seikoh Horiuchi, Nobuhiro Yamada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)790-794
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume316
Issue number3
DOIs
StatePublished - 2004/04/09

Keywords

  • ATP-binding-cassette transporter A1
  • Macrophage
  • Reverse cholesterol transport
  • Statins (HMG-CoA reductase inhibitors)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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