ATP binding cassette Al (ABCAl) 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 ABCAl-mediated efflux from Fu5AH rat hepatoma cells, that here we demonstrate to express functional ABCAl upon treatment with 220H/cRA. In both basal and ABCAl expressing cells pitavastatin 0.1-50 muM 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. (C) 2004 Elsevier Inc. All rights reserved.