Pitavastatin increases ABCA1-mediated lipid efflux from Fu5AH rat hepatoma cells.
ATP binding cassette A1 (ABCA1) is responsible in vivo for the formation of HDL by promoting the lipidation of apoprotein A-I (apoA-I) via cholesterol and phospholipid efflux from the liver. Treatment of patients with statins produces an increase in HDL plasma level, but the underlying mechanism is not completely understood. In this work we investigated the ability of pitavastatin to modulate ABCA1-mediated efflux from Fu5AH rat hepatoma cells, that here we demonstrate to express functional ABCA1 upon treatment with 22OH/cRA. In both basal and ABCA1 expressing cells pitavastatin 0.1-50microM induced a dose-dependent increase in cholesterol efflux to apoA-I; this effect was reversed by mevalonate or geranyl geraniol. A stimulatory effect was also observed on phospholipid efflux. Similar results were obtained with compactin, suggesting a class-related effect of statins. These results indicate a potential mechanism for the improvement in HDL plasma profile observed in patients treated with statins.
Zanotti
Ilaria
I
Department of Pharmacological and Biological Sciences, and Applied Chemistries, University of Parma, Viale delle Scienze 27/A, 43100 Parma, Italy.
Favari
Elda
E
Sposito
Andrei C
AC
Rothblat
George H
GH
Bernini
Franco
F
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004224:Diterpenes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004224:Diterpenes; D004791:Enzyme Inhibitors; D011804:Quinolines; D002784:Cholesterol; C017338:geranylgeraniol; C108475:pitavastatin; D008798:Mevalonic Acid