[Fluvastatin affects HLA class I expression on endothelial cells].
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 IFNgamma. Primary cultures of human ECs have been treated with increasing doses of fluvastatin (0.01; 0.1 and 1 microM) with or without IFNgamma 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 IFNgamma. These effects are reversed by mevalonate. In conclusion, our results suggest that while decreasing MHC class II expression, fluvastatin (at 0.1 and 1 microM) 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.
Belliard
Guillaume
G
Institut national de la santé et de la recherche médicale, UMR 643, Immunointervention en allo et xénotransplantation, et institut de transplantation et de recherche en transplantation, CHU Hôtel-Dieu, 44093 Nantes cedex 01, France.
Coupel
Stéphanie
S
Charreau
Béatrice
B
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology
D005229:Fatty Acids, Monounsaturated; D015395:Histocompatibility Antigens Class I; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D007371:Interferon-gamma