title: Statins downregulate ATP-binding-cassette transporter A1 gene expression in macrophages.
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.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Miao
authors.initials: M
authors.lastname: Shu
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakakuki
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Takahashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sakai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Yokoo
authors.forename: Ken
authors.initials: K
authors.lastname: Matsuzaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kaoruko Tada
authors.initials: KT
authors.lastname: Iida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Toyoshima
authors.forename: Seikoh
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D000069059:Atorvastatin; D001692:Biological Transport; D015152:Blotting, Northern; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D041701:Swiss 3T3 Cells; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D012333:RNA, Messenger; D000077340:Fluvastatin; D002784:Cholesterol; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D008156:Luciferases; D010100:Oxygen