Effet de la fluvastatine sur l'expression du CMH de classe I par les cellules endothéliales humaines

Abstract

Originally designed to target elevated lipids, the “traditional” cause of atherosclerosis, statins might also confer vascular benefit by directly or indirectly modulating both the inflammatory and immune responses. Statins have been shown to downregulate MHC class II and CD40 expression on activated endothelial cells (EC). In this study, we investigate the potential effect of statins on MHC class I expression and regulation in response to IFNγ. Primary cultures of human ECs have been treated with increasing doses of fluvastatin (0.01; 0.1 and 1 μM) with or without IFNγ for 48 hours. Surface expression of MHC class I and class II has been analyzed by flow cytometry. Our data indicate that fluvastatin increases MHC class I expression on quiescent ECs by a dose-dependent effect. Furthermore, fluvastatin potentiates the MHC class I upregulation but prevents MHC class II induction triggered by IFNγ. These effects are reversed by mevalonate. In conclusion, our results suggest that while decreasing MHC class II expression, fluvastatin (at 0.1 and 1 μM) upregulates MHC class I expression on ECs. Functional consequences of statin-mediated modulation of MHC on ECs have still to be elucidated in vitro and in vivo.