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

• 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
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.02.121

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.