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 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.
Sone
Hirohito
H
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Shimano
Hitoshi
H
Shu
Miao
M
Nakakuki
Masanori
M
Takahashi
Akimitsu
A
Sakai
Masakazu
M
Sakamoto
Yuichiro
Y
Yokoo
Tomotaka
T
Matsuzaka
Ken
K
Okazaki
Hiroaki
H
Nakagawa
Yoshimi
Y
Iida
Kaoruko Tada
KT
Suzuki
Hiroaki
H
Toyoshima
Hideo
H
Horiuchi
Seikoh
S
Yamada
Nobuhiro
N
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
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