Mycophenolate mofetil prevents the development of experimental autoimmune myocarditis

J Mol Cell Cardiol. 2005 Sep;39(3):467-77. doi: 10.1016/j.yjmcc.2005.04.004.


Experimental autoimmune myocarditis (EAM) is characterized by the appearance of multinucleated giant cells. EAM leads to severe myocardial damage and is a useful model of human giant cell myocarditis. We investigated whether mycophenolate mofetil (MMF), which is a potent immunosuppressant, prevents the development of myocarditis in a rat EAM model, and focused on the role of osteopontin (OPN) in the pathogenesis of this disorder. Adult Lewis rats were immunized with porcine cardiac myosin to establish EAM. The early MMF treatment completely prevented the development of EAM, and the late MMF treatment was also effective even against established EAM. Echocardiogram demonstrated that left ventricular function was also improved by the treatment with MMF. Real-time RT-PCR analysis showed that both early and late MMF treatments significantly inhibited myocarditis-induced OPN mRNA expression in the heart. Immunohistochemistry revealed that OPN expression was prominent in the myocardium on day 14, whereas expression was observed in the infiltrated macrophages on day 21. Mycophenolic acid (MPA) did inhibit agonist-induced OPN expression in cultured cardiomyocytes. These results show the therapeutic potential of MMF for autoimmune myocarditis and provide new insights into the pathogenesis of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology*
  • Autoimmune Diseases / physiopathology*
  • Body Weight
  • Cells, Cultured
  • Disease Models, Animal
  • Echocardiography
  • Heart Ventricles / cytology
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Myocarditis / drug therapy
  • Myocarditis / immunology
  • Myocarditis / pathology
  • Myocarditis / physiopathology
  • Myocarditis / prevention & control*
  • Myocardium / metabolism
  • Myocytes, Cardiac / drug effects
  • Organ Size
  • Osteopontin
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / metabolism
  • Time Factors


  • Immunosuppressive Agents
  • RNA, Messenger
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, rat
  • Osteopontin
  • Mycophenolic Acid