Submitted on June 1, 2007
Revised on January 15, 2008
Accepted on February 5, 2008
The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential
Ilaria Zanotti, Francesco Potì, Matteo Pedrelli, Elda Favari, Elsa Moleri, Guido Franceschini, Laura Calabresi, and Franco Bernini
Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma 43100
Corresponding Author: fbernini{at}unipr.it
The Liver-X-Receptors (LXR) have shown to affect lipoprotein plasma profile, lipid metabolism and the reverse cholesterol transport (RCT). In the present study we investigated whether a short term administration of the synthetic LXR agonist T0901317 (T0) to mice may affect RCT by modulating the capacity of plasma to promote cellular lipid efflux. Consistent with previous data, the pharmacological treatment of mice caused a significant increase of macrophage-derived [3H]-cholesterol content in plasma, liver and feces and resulted in improved capacity of plasma to promote cellular cholesterol release through passive diffusion and Scavenger Receptor Class B Type I (SR-BI)-mediated mechanisms. Differently, plasma from treated mice possessed similar or reduced capacity to drive lipid efflux via ATP Binding Cassette A1 (ABCA1). Consistent with these data, the analysis of plasma HDL fractions revealed that T0 caused the formation of larger, lipid enriched particles. These results suggest that T0 promotes in vivo RCT from macrophages at least in part by inducing an enrichment of those HDL subclasses that increase plasma capacity to promote cholesterol efflux by passive diffusion and SR-BI-mediated mechanisms.
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