Immunoregulatory effects of atorvastatin on the MHC class II molecule expression by myocardium in experimental autoimmune myocarditis
To explore the immunoregulalory effects of atorvastatin, 3-hydroxy-3-methyl-glu-taryl coenzyme A (HMG-CoA) reductase inhibitor, on the expression of MHCⅡ molecules in experimental autoimmune myocarditis (EAM), and to explore the therapeutic potential for EAM. Methods Myocarditis was induced in Lewis rats by the injection of porcine cardiac myosin. Atorvastatin (10 mg/kg each day) or vehicle was orally administered for 3 weeks. Twenty one days after immunization, echocardiography was examined and the severity of myocarditis was evaluated histopathologically. Immunohistochemistry techniques were used to distinguish the CD4~+ or CDS~+ T lymphocytes and to evaluate the expression of MHC Ⅱ molecules in the myocardium. TypeⅠ,Ⅲ and Ⅳ CⅡ TA promoter transcription was compared by RT-PCR. Results Cardiac function was improved in the ator-vastatin-treated group compared to the untreated one. In atorvastatin group, histological severity of myocarditis was attenuated, and the expression of MHC Ⅱ molecules in the "nonprofessional" APC in the myocardium was reduced. Transcription of typeⅣ CⅡTA promoter was down-regulated in the atorvastatin-treated group, but typeⅠ ,Ⅲ CⅡTA promoter mRNA were not statistically different. Conclusion Atorvastatin ameliorates cardiac function and inflammatory reaction of the myocardium in EAM, and so HMG-CoA reductase blockade may be a promising new strategy for the treatment of organ specific autoimmune myocardial impairment.