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Contibution of cardiomyocyte apoptosis to development of congestive heart failure

Research Project

Project/Area Number 12670645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionFirst Department of Internal Medicine, Yamagata University School of Medicine

Principal Investigator

YAMAGUCHI Seiji  Yamagata University of School of Medicine, Assistant Professor, 医学部, 講師 (30239892)

Co-Investigator(Kenkyū-buntansha) YOSHIMURA Tetsuhiko  Institute for Life Support Technology Yamagata Public Corporation for the Development of Industry, Director of Research, 生物ラジカル研究所, 部長 (70271517)
SATA Makoto  Yamagata University of School of Medicine, Instructor, 医学部, 講師 (00280892)
TAKEISHI Yasuchika  Yamagata University of School of Medicine, Assistant Professor, 医学部, 講師 (40272067)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsFas / Fas Ligand / apoptosis / cardiomyocyte / heart failure / doxorubicin / FLIP / Reactive oxygen species / doxorubinlin / reactive oxygen species
Research Abstract

Apoptosis plays a pivotal role in loss of cells not only during physiological phenomena, such as normal turnover of tissues, but also in many pathophysiological phenomena. Evidence is accumulating that the apoptotic mechanism is involved in various heart disorders. The Fas/FasL system has been reported to be activated in human heart failure. We observed that cardiomyocyte was generally resistant to Fas-mediated apoptosis in vitro; however, after treatment of sublethal dose of doxorubicin, cardiomyocyte apoptosis was dramatically facilitated by recombinant FasL. This finding is intriguing, because the doxorubicin-induced sensitivity to Fas in cardiomyocyte can be induced by a molecule which may be a target for treating doxorubicin-associated cardiomyopathy. Recently, FLICE-inhibitory protein (FLIP), a molecule with sequence homology to caspase-8 (FLICE), was identified as an anti-apoptotic protein. FLIP is capable of binding FADD, yet is unable to be cleaved to an active caspase-8, thus shutting off the initiation of the death pathway. We observed whether FLIP levels are related to the doxorubicin-induced sensitivity to Fas in cultured neonatal rat cardiomyocyte. Moreover, the expression of FLIP was down-regulated by oxidative stress. FLIP may be a therapeutic target for Dox-induced cardiomyopathy.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report

Research Products

(12 results)

All Other

All Publications (12 results)

  • [Publications] Fujiwara S, et al.: "Reverse redistribution of ^<99m>Tc-sestamibi after direct percutancous transluminal coronayt angioplasty in acute myocardial infarction : relationship with wall motion and functional response to dobutamine stimulation"Nucl Med Commun. 22. 1223-1230 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirakabe M, et al.: "Impaired distensibility of the left ventricle after stiffening of the right ventricle"J Appl Physiol. 91. 435-440 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamaoka M, Yamaguchi S, Suzuki T, Okuyama M, Nitobe J, Nakamura N, Mitsui- Y, Tomoike H: "Apoptosis in rat cardiac myocytes induced by Fas ligand: priming for Fas-mediated apoptosis with doxorubicin"J Mol Cell Cardiol. 32(6). 881-889 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okuyama M, Yamaguchi S, Yamaoka M, Nitobe J, Fujii S, Yoshimura T, Tomoike H: "Nitric oxide enhances expression and shedding of tumor necrosis factor receptor I (p55) in endothelial cells"Arterioscler Thromb Vasc Biol. 20(6). 1506-1511 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirakabe M, Yamaguchi S, Tamada Y, Baniya G, Fuku Miyawaki H, Tomoike T: "Impaired Distensibility of the L Ventricle After Stiffening of the Right Ventricle"J Appl Physiol. 91(1). 435-440 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiwara S, Takeishi Y, Hirono O, Fukui A, Okuyama, Yamaguchi S, Ito M, Kaneko K, Shishido T, Miyamoto , Yuki K, Miyashita T, Takahashi K, Minamihaba O, Tomo H: "Reverse Redistribution of Technetium-99m-Sestam after Direct PTCA in Acute Myocardial Infarcti Relatioship with Wall Motion and Functional Response Dobutamine Stimulation"Nuclear Med Communications. 22. 1223-30 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] The EPOCH Study Group: "Effects of Pimobendan on Adverse Cardiac Events and Physical Activities in Patients with Mild to Moderate Chronic Heart Failure - The Effect of Pimobendan on Chronic Heart Failure Study (EPOCH Study)"Circ J (Participating Investigator). 66. 149-157 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiwara S., et al.: "Reverse redistribution of ^<99m>Tc-sestamibi after direct percutaneous transluminal coronary angioplasty in acute myocardial infarction:relationship with wall motion and functional response to dobutamine stimulation"Nucl Med Commun. 22. 1223-1230 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shirakabe M., et al.: "Impaired distensibility of the left ventricle after stiffening of the right ventricle"J Appl Physiol. 91. 435-440 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shirakabe M. et al: "Distensibility after stiffening right ventricle -Myocardial stretch due to Ventricular Deformation-"J Appl Physiol. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okuyama M. et al: "Nitric oxide enhances expression and shedding of tumor neurosis factor receptor I (p55) in endothelial cells."Arterioscler Thromb Vasc Biol. 20. 1506-1511 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaoka M et al: "Apoptosis in rat cardiac myocytes induced by Fas ligand : priming for Fas-mediated apoptosis with doxorubilin"J mol Cell Cardiol. 32(6). 881-889 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-03-31   Modified: 2016-04-21  

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