Skip to main content
SpringerLink
Log in

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

  • Conference paper
Heart Failure

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sekiguchi M, Hiroe M, Take M, Hirosawa K (1980) Clinical and histopathological profile of the sarcoidosis of heart and acute idiopathic myocarditis. Concepts through a study employing endomyocardial biopsy II. Myocarditis. Jpn Circ J 44: 264–273

    Article  PubMed  CAS  Google Scholar 

  2. Hiroe M, Sekiguchi M, Take M, Matsuda M, Hirosawa K (1985) Hemodynamic studies and response to a combined therapy of nitroglycerin ointment and dopamine in patients with acute myocarditis. Heart Vessels Suppl 1: 180–186

    Article  PubMed  CAS  Google Scholar 

  3. Hiroe M, Sekiguchi M, Take M, Kusakabe K, Shigeta A, Hirosawa K (1985) Long follow-up study in patients with prior myocarditis by radionuclide methods. Heart Vessels Suppl 1: 199–203

    Article  PubMed  CAS  Google Scholar 

  4. Dec GW, Alacios IF, Fallon JT, Artez HT, Mills J, Lee DC, Johnson RA (1985) Active myocarditis in the spectrum of acute dilated cardiomyopathies: clinical features, histologic correlates, and clinical outcome. N Engl J Med 312: 885–890

    Article  PubMed  Google Scholar 

  5. Fenoglio JJ, Ursell PC, Kellogg CF, Drusin RE, Weiss MB (1983) Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med 308: 112–118

    Article  Google Scholar 

  6. Aretz JT (1987) Myocarditis: the Dallas criteria. Hum Pathol 18: 619–635

    Article  PubMed  CAS  Google Scholar 

  7. Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL (1991) Clinico-pathologic description of myocarditis. J Am Coll Cardiol 18: 1617–1626

    Article  PubMed  CAS  Google Scholar 

  8. Woodruff JF (1980) Viral myocarditis: a review. Am J Pathol 101: 427–484

    Google Scholar 

  9. Bowles NE, Richardson Pi Olsen EGJ,Archard LC (1986) Detection of Coxsackie-Bvirus specific RNA sequence in myocardial biopsy sample from patients with myocarditis and dilated cardiomyopathy. Lancet 1: 1120–1123

    Article  PubMed  CAS  Google Scholar 

  10. Jin O, Sole M, Butany J (1990) Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using polymerase chain reaction. Circulation 82: 8–16

    Article  PubMed  CAS  Google Scholar 

  11. Martin AB, Webber S, Fricker J, Jaffe R, Demmler G, Kearney D, Zhang Y-H, Bodurtha J, Gelb B, Ni J, Bricker T, Towbin JA (1994) Acute myocarditis: rapid diagnosis by PCR in children. Circulation 90: 330–339

    PubMed  CAS  Google Scholar 

  12. Berke G (1995) The CTL’s kiss of death. Cell 81: 9–12

    Article  PubMed  CAS  Google Scholar 

  13. Liu CC, Young LHY, Young JDE (1996) Lymphocyte-mediated cytolysis and disease. N Engl J Med 335: 1651–1659

    Article  PubMed  CAS  Google Scholar 

  14. Kâgi D, Vignaux F, Ledeman B, Burki K, Depraetere V, Nagata S, Hengarttner H. Golstein P (1994) Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265: 528–530

    Article  PubMed  Google Scholar 

  15. Young JD, Hengartner H, Podack ER, Cohn ZA (1986) Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 44: 849–859

    Article  PubMed  CAS  Google Scholar 

  16. Shi L, Kam C-M, Powers JC, Aebersold R, Greenberg AH (1992) Purification of three cytotoxic lymphocytes granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. J Exp Med 176: 1521–1529

    Article  PubMed  CAS  Google Scholar 

  17. Arase H, Arase N, Saito S (1995) Fas-mediated cytotoxicity by freshly isolated natural killer cells. J Exp Med 181: 1235–1238

    Article  PubMed  CAS  Google Scholar 

  18. Nagata S (1997) Apoptosis by death factor. Cell 88: 355–365

    Article  PubMed  CAS  Google Scholar 

  19. Krammer PH, Dhein J, Walczak H, Behrmann I, Mariani S, Matiba B, Fath M, Daniel PT, Knipping E, Westendorp MO, Stricker K, Baumler C, Hellbardt S, Germer M, Peter ME, Debatin K-M (1994) The role of APO-1 mediated apoptosis in the immune system. Immunol Rev 142: 175–191

    Article  PubMed  CAS  Google Scholar 

  20. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257

    Article  PubMed  CAS  Google Scholar 

  21. Li Y, Sharov VG, Jiang N, Zaloga C, Sabbah HN, Chopp M (1995) Ultrastructual and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146: 1045–1051

    PubMed  CAS  Google Scholar 

  22. Majino G, Joris I (1995) Apoptosis, oncosis, and necrosis: an overview of cell death. Am J Pathol 146: 3–15

    Google Scholar 

  23. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous nuclease activation. Nature 284: 555–556

    Article  PubMed  CAS  Google Scholar 

  24. Wyllie AH, Morris RG, Smith AL, Dunlop D (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macro-molecular synthesis. J Pathol 142: 67–77

    Article  PubMed  CAS  Google Scholar 

  25. Raff MC (1992) Social control on cell survival and cell death. Nature 356: 397–400

    Article  PubMed  CAS  Google Scholar 

  26. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of diseases. Science 267: 1456–1462

    Article  PubMed  CAS  Google Scholar 

  27. Feuerstein G, Rufflo RR Jr, Yue TL (1997) Apoptosis and congestive heart failure. Trends Cardiovasc Med 7: 249–255

    Article  PubMed  CAS  Google Scholar 

  28. MacLellan WR, Schneider MD (1997) Death design: programmed cell death in cardiovascular biology and disease. Circ Res 81: 137–144

    PubMed  CAS  Google Scholar 

  29. Haunstetter A, Izumo S (1998) Apoptosis: basic mechanisms and implications for cardiovascular diseases. Circ Res 82: 1111–1126

    PubMed  CAS  Google Scholar 

  30. Anversa P, Leri A, Beltrami CA, Guerra S, Kajstura J (1998) Myocyte death and growth in the failing heart. Lab Invest 78: 767–786

    PubMed  CAS  Google Scholar 

  31. Sabbah H, Sharov VG (1998) Apoptosis in heart failure. Prog Cardiovasc Dis 40: 549–562

    Article  PubMed  CAS  Google Scholar 

  32. Kajstura J, Mansukhan IM, Cheng W, Reis Anversa P (1995) Programmed cell death and the expression of the protooncogene Bel-2 in myocyte during postnatal maturation of the heart. 219: 110–121

    CAS  Google Scholar 

  33. Takeda K, Yu ZX, Nishikawa T, Tanaka M, Hosoda S, Ferrans VJ, Kasajima T (1996) Apoptosis and DNA fragmentation in the bulbus cordis of the developing rat heart. J Mol Cell Cardiol 28: 209–215

    Article  PubMed  CAS  Google Scholar 

  34. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw B-A (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 335: 1182–1189

    Article  PubMed  CAS  Google Scholar 

  35. Olivetti JT, Abbi R, Quaini F, Kajstura J, Cheng W, Wuaini E, Loreto CD, Beltrrrami CA, Krajewski S, Reed JC, Anversa P (1997) Apoptosis in failing human heart. N Engl J Med 336: 1131–1141

    Article  PubMed  CAS  Google Scholar 

  36. Liu Y, Cigola E, Cheng E, Kajstura J, Olivetti G, Hintze TH, Anversa P (1995) Myocyte nuclear mitotic division and programmed cell death characterize the cardiac myopathy induced by rapid right ventricular pacing in dogs. Lab Invest 73: 771–787

    PubMed  CAS  Google Scholar 

  37. Sharov VG, Sabbah HN, Shimoyama H, Goussev AV, Lesch M, Goldstein S (1996) Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 148: 141–149

    PubMed  CAS  Google Scholar 

  38. Bing OHL (1994) Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure overload. J Mol Cell Cardiol 26: 943–948

    Article  PubMed  CAS  Google Scholar 

  39. Itoh G, Tamura J, Suzuki M, Suzuki Y, Ikeda H, Koike M, Nomura M, Jie T, Ito K (1995) DNA fragmentation of human infarcted myocardial cells demonstrated by the nick end labeling method and DNA agarose gel electrophoresis. Am J Pathol 146: 1325–1331

    PubMed  CAS  Google Scholar 

  40. Saraste AK, Pulkki K, Henrikesen M, Parvinen M, Voipio-Pulkki L-M (1997) Apoptosis in human acute myocardial infarction. Circulation 95: 320–323

    PubMed  CAS  Google Scholar 

  41. Gottlieb RA, Burleson KO. Kloner RA, Bablor BM, Engler RL (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94: 1621–1628

    Article  PubMed  CAS  Google Scholar 

  42. Fliss H, Gattinger D (1996) Apoptosis in ischemic and reperfused rat myocardium. Circ Res 79: 949–956

    PubMed  CAS  Google Scholar 

  43. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P (1996) Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest 74: 86–107

    PubMed  CAS  Google Scholar 

  44. Fliss H, Gattinger D (1996) Apoptosis in ischemia and reperfused rat myocardium. Circ Res 79: 949–956

    PubMed  CAS  Google Scholar 

  45. Mallat Z, Tedgui A, Fontaliran F, Frank R, Durigon M, Fontaine G (1996) Evidence of apoptosis in arrhythmogenic right ventricular dysplasia. N Engl J Med 335: 1190–1196

    Article  PubMed  CAS  Google Scholar 

  46. Valente M, Calabrese F, Thiene G. Angnelini A, Basso C, Nava A, Rossi L (1998) In vivo evidence of apoptosis in arrhythmogenic right ventricular cardio-myopathy. Am J Pathol 132: 479–484

    Google Scholar 

  47. James TN, Nichols MM, Sapire DW, DiPatre PL, Lopez SM (1996) Complete heart block and fatal right ventricular failure in an infant. Circulation 93: 1588–1600

    PubMed  CAS  Google Scholar 

  48. Diez J, Panizo A, Hernandez M, Vega F. Sola I, Fortufio MA, Pardo J (1997) Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension 30: 1029–1034

    PubMed  CAS  Google Scholar 

  49. Frusutaci A, Chimenti C, Setoguchi M, Guerra S, Corsello S, Crea F, Len A, Kajstura J, Anversa P, Maseri A (1999) Cell death in acromegalic cardiomyopathy. Circulation 99: 1426–1434

    Google Scholar 

  50. Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, Marumo H, Hiroe M (1994) Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75: 426–433

    PubMed  CAS  Google Scholar 

  51. Laderoute KR, Webster KA (1997) Hypoxia/reoxygenation stimulate Jun kinase activity through redox signaling in cardiac myocytes. Circ Res 80: 336–344

    PubMed  CAS  Google Scholar 

  52. Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze TH, Olivetti G, Anversa P (1995) Stretch-induced programmed myocyte cell death. J Clin Invest 96: 2247–2259

    Article  PubMed  CAS  Google Scholar 

  53. Krown KA, Page MT, Nguyen C, Zechner D, Gutierrez V, Comstock KL, Glembotski CC, Quintana PJE, Sabbadini RA (1996) Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 98: 2854–2856

    Article  PubMed  CAS  Google Scholar 

  54. Kajstura J, Cigola E, Malhotra A, Cheng W, Meggs LG, Anversa P (1997) Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol 29: 859–870

    Article  PubMed  CAS  Google Scholar 

  55. Wu CF, Bishopric NH, Pratt RE (1997) Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. J Biol Chem 272: 14860–14866

    Article  PubMed  CAS  Google Scholar 

  56. Aikawa R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Tanaka M, Shiojima I, Hiroi Y, Yazaki Y (1997) Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100: 1813–1821

    Article  PubMed  CAS  Google Scholar 

  57. Shimojo T, Hiore M, Ishiyama S, Ito H, Nishikawa T, Marumo F (1999) Nitric oxide induces apoptotic death of cardiomyocytes via a cyclic-GMP-dependent pathway. Exp Cell Res 247: 38–47

    Article  PubMed  CAS  Google Scholar 

  58. Watanabe FR, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S (1992) The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 148: 1274–1279

    Google Scholar 

  59. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66: 233–243

    Article  PubMed  CAS  Google Scholar 

  60. Yonehara S, Ishi A, Yonehara M (1989) A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 169: 1747–1756

    Article  PubMed  CAS  Google Scholar 

  61. Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y, Itoh N, Suda T, Nagata S (1993) Lethal effect of the anti-Fas antibody in mice. Nature 364: 306–309

    Article  Google Scholar 

  62. Suda T, Nagata S (1994) Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med 179: 873–879

    Article  PubMed  CAS  Google Scholar 

  63. Dhein J, Walczak H, Bâumler C, Debatin KM, Krammer PH (1995) Autocrine T-cell suicide mediated by Apo-1/Fas/CD95. Nature 373: 438–441

    Article  PubMed  CAS  Google Scholar 

  64. Ju S-T, Panka DJ, Cui H, Ettinger R, El-Khatib M, Sherr DH, Stanger BZ, MarshakRothstein A (1995) Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373: 444–448

    Article  PubMed  CAS  Google Scholar 

  65. Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263: 1759–1762

    Article  PubMed  CAS  Google Scholar 

  66. Liu C, Cheng J, Mountz JD (1995) Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation. Biochem J 310: 957–963

    PubMed  CAS  Google Scholar 

  67. Papoff G, Cascino I, Eramo A, Starace G, Lynch DH, Ruberti G (1996) An N-terminal domain shared by Fas/Apo-1(CD95) soluble variants prevents cell death in vitro. J Immunol 156: 4622–4630

    PubMed  CAS  Google Scholar 

  68. Nishigaki K, Minatoguchi S, Seishima M, Asano K, Noda T, Yasuda N, Sano H, Kumada H, Takemura M, Noma A, Tanaka T, Watanabe S, Fujiwara H (1997) Plasma Fas ligand, an inducer of apoptosis, and plasma soluble Fas, an inhibitor of apoptosis, in patients with chronic congestive heart failure. J Am Coll Cardiol 29: 1214–1220

    Article  PubMed  CAS  Google Scholar 

  69. Okuyama M, Yamaguchi S, Nozaki N, Yamaoka M, Shirakabe M, Tomoike H (1997) Serum levels of soluble form of Fas molecule in patients with congestive heart failure. Am J Cardiol 79: 1698–1701

    Article  PubMed  CAS  Google Scholar 

  70. Toyozaki T, Hiroe M, Saito T, Iijima Y. Takano H, Hiroshima K, Kohno H, Ishiyama S, Marumo F, Masuda Y, Ohwada H (1998) Levels of soluble Fas in patients with myocarditis, heart failure of unknown origin, and in healthy volunteers. Am J Cardiol 81: 798–800

    CAS  Google Scholar 

  71. Kayagaki N, Kawasaki A, Ebata T. Ohmoto H, Ikeda S, Inoue S, Yoshini K, Nozawa K, Okuyama K, Yagita H (1995) Metalloproteinase-mediated release of human Fas ligand. J Exp Med 182: 1777–1783

    CAS  Google Scholar 

  72. Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F, Motoyoshi K, Mizuki M, Tagawa S, Ohga S, Hatake K, Drummoud AH, Nagata S (1996) Fas ligand in human serum. Nature Med 2: 317–322

    Article  PubMed  CAS  Google Scholar 

  73. Nozawa K, Kayagaki N,Tokano Y, Yagita H, Okumura K, Hashimoto H (1997) Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases. Arthritis Rheum 40: 1126–1129

    CAS  Google Scholar 

  74. Tanaka M, Suda T, Takahashi T, Nagata S (1995) Expression of the functional soluble form of human Fas ligand in activated lymphocytes. EMBO J 14: 1129–1135

    PubMed  CAS  Google Scholar 

  75. Toyozaki T, Hiroe M, Tanaka M, Nagata S, Ohwada H, Marumo F (1998) Levels of soluble Fas ligand in myocarditis. Am J Cardiol 82: 246–248

    Article  PubMed  CAS  Google Scholar 

  76. Neu N, Rose NR, Beisel KW, Herskowitz A, Gurri-Glass G, Craig SW (1987) Cardiac myosin induces myocarditis in genetically predisposed mice. J Immunol 139: 3630–3636

    PubMed  CAS  Google Scholar 

  77. Smith SC, Allen PM (1991) Myosin-induced acute myocarditis is a T cell-mediated disease. J Immunol 147: 2141–2147

    PubMed  CAS  Google Scholar 

  78. Kodama M, Matsumoto Y, Fujiwara M (1992) In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis. Circulation 85: 1918–1926

    PubMed  CAS  Google Scholar 

  79. Ishiyama S, Hiroe M, Nishikawa T, Abe S, Shimojo T, Ito H, Ozasa S, Yamakawa K, Matsuzaki M, Mohammed MU, Nakazawa H, Kasajima T, Marumo F (1997) Nitric oxide contributes to the progression of myocardial damage in experimental autoimmune myocarditis in rats. Circulation 95: 489–496

    PubMed  CAS  Google Scholar 

  80. Davidoff R, Palacios I, Southern J, Fallon JT, Newell J, Dec GW (1991) Giant cell versus lymphocytic myocarditis: a comparison of their clinical features and long-term outcomes. Circulation 83: 953–961

    PubMed  CAS  Google Scholar 

  81. Ishiyama S, Hiroe M, Nishikawa T, Shimojo T, Abe S, Fujisaki H, Ito H, Yamakawa K, Kobayashi N, Kasajima T, Marumo F (1998) The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats. J Immunol 161: 4695–4701

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Second Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-0014, Japan

    Michiaki Hiroe

  2. Division of Pathology, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, Chiba, Japan

    Tetsuya Toyozaki

Authors
  1. Michiaki Hiroe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tetsuya Toyozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, 068-8638, Kita-ku, Sapporo, Japan

    Akira Kitabatake M.D., Ph.D. (Director and Chairman) & Hiroshi Okamoto M.D., Ph.D. (Associate Professor) (Director and Chairman) &  (Associate Professor)

  2. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, 606-8507, Sakyo-ku, Kyoto, Japan

    Shigetake Sasayama M.D., Ph.D. (Director and Chairman) (Director and Chairman)

  3. Coronary and Intensive Care Unit, The Cleveland Clinic Foundation, USA

    Gary S. Francis M.D. (Director, Professor of Medicine) (Director, Professor of Medicine)

  4. Department of Cardiology, Ohio State University, F25, 9500 Euclid Avenue, 44195, Cleveland, OH, USA

    Gary S. Francis M.D. (Director, Professor of Medicine) (Director, Professor of Medicine)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Tokyo

About this paper

Cite this paper

Hiroe, M., Toyozaki, T. (2000). Pathogenesis of Myocardial Injury and Cell Death in Myocarditis: Its Relation to the Fas/Fas Ligand Pathway. In: Kitabatake, A., Sasayama, S., Francis, G.S., Okamoto, H. (eds) Heart Failure. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68331-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-68331-5_5

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68333-9

  • Online ISBN: 978-4-431-68331-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation