Pitavastatin increases ABCA1-mediated lipid efflux from Fu5AH rat hepatoma cells |
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Authors: | Zanotti Ilaria Favari Elda Sposito Andrei C Rothblat George H Bernini Franco |
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Affiliation: | Department of Pharmacological and Biological Sciences, and Applied Chemistries, University of Parma, Viale delle Scienze 27/A, 43100 Parma, Italy. |
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Abstract: | 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. |
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Keywords: | ABCA1 Cholesterol efflux Fu5AH Geranyl geraniol LXR Mevalonate Pitavastatin |
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