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

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 s...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-04, Vol.316 (3), p.790-794
Main Authors: Sone, Hirohito, Shimano, Hitoshi, Shu, Miao, Nakakuki, Masanori, Takahashi, Akimitsu, Sakai, Masakazu, Sakamoto, Yuichiro, Yokoo, Tomotaka, Matsuzaka, Ken, Okazaki, Hiroaki, Nakagawa, Yoshimi, Iida, Kaoruko Tada, Suzuki, Hiroaki, Toyoshima, Hideo, Horiuchi, Seikoh, Yamada, Nobuhiro
Format: Article
Language:English
Subjects:
Animals
Atorvastatin Calcium
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - chemistry
ATP-Binding Cassette Transporters - physiology
ATP-binding-cassette transporter A1
Biological Transport
Blotting, Northern
Cell Line
Cholesterol - metabolism
Dose-Response Relationship, Drug
Fatty Acids, Monounsaturated - pharmacology
Heptanoic Acids - pharmacology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Indoles - pharmacology
Lovastatin - pharmacology
Luciferases - metabolism
Macrophage
Macrophages - metabolism
Mice
Oxygen - metabolism
Promoter Regions, Genetic
Pyrroles - pharmacology
Reverse cholesterol transport
RNA, Messenger - metabolism
Simvastatin - pharmacology
Statins (HMG-CoA reductase inhibitors)
Swiss 3T3 Cells
Time Factors
Transcription, Genetic
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.02.121