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Pathogenesis of Myocardial Injury and Cell Death in Myocarditis: Its Relation to the Fas/Fas Ligand Pathway

  • Michiaki Hiroe
  • Tetsuya Toyozaki
Conference paper

Abstract

The Fas/APO-1(CD95) cell surface receptor binds to the Fas ligand, leading to apoptotic cell death under a variety of pathological conditions. In viral myocarditis, a perforin-based mechanism involving killer cells is known to play a role in necrotic myocardial injury. However, little is known about apoptotic cell death in myocarditis. Serum levels of the soluble form of Fas and Fas ligand were much higher in patients with myocarditis than in other cardiac patients. There was a positive correlation between sIL-2R and sFas levels in patients with myocarditis. In the myocarditis group, sFasligand levels increased with the severity of heart failure, as defined by New York Heart Association functional class. Cardiac tissues from rats with autoimmune myocarditis showed in situ DNA fragments by DNA laddering formation and TUNEL assay, the biological hallmark of apoptosis, in some cardiomyocytes and infiltrating lymphocytes. The expression of Fas ligand was up-regulated in some cardiomyocytes and lymphocytes. Fas ligand mRNA and protein were expressed in some CD4+ T cells. Coexpression of Fas with the Fas ligand was observed in some infiltrating lymphocytes. Furthermore, when cultured neonatal cardiomyocytes were exposed to the soluble form of Fas ligand in the presence of actinomycin D, the cells underwent apoptotic cell death, as demonstrated by electron microscopy, flow cytometry, and the TUNEL assay. These results suggest that some portion of the cardiomyocytes and infiltrating lymphocytes are subjected to apoptotic cell death, possibly due to T cell-mediated cytotoxicity, which is modulated by the Fas/Fas ligand pathway in myocarditis.

Key words

Apoptosis Myocarditis Fas/Fas ligand pathway TUNEL assay Electron microscopy Flow cytometry 

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Copyright information

© Springer-Verlag Tokyo 2000

Authors and Affiliations

  • Michiaki Hiroe
    • 1
  • Tetsuya Toyozaki
    • 2
  1. 1.Division of Cardiology, Second Department of Internal MedicineTokyo Medical and Dental UniversityBunkyo-ku, TokyoJapan
  2. 2.Division of Pathology, Institute of Pulmonary Cancer ResearchChiba University School of MedicineChibaJapan

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