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Soluble Fas, an inhibitor of apoptosis, gene therapy using adenovirus vector for chronic congestive heart failure

Research Project

Project/Area Number 13670698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionGifu University

Principal Investigator

NISHIGAKI Kazuhiko  University Hospital, Lecturer, 医学部附属病院, 講師 (60198447)

Co-Investigator(Kenkyū-buntansha) FUJIWARA Hisayoshi  School of Medicine, Professor, 大学院・医学研究科, 教授 (80115930)
KOSAI Kenichiro  School of Medicine, Associate Professor, 医学部, 助教授 (90258418)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordssFas gene therapy / heart failure / UM-X 7.1 hamster / apoptosis / necrosis / serum sFas / ventricular dilatation / fibrosis / 遺伝子治療 / 血漿可溶性Fas
Research Abstract

Serum soluble Fas (sFas) can block the binding between Fas-ligand and Fas-receptor on cell membrane, and is an inhibitor of apoptosis. SFas gene therapy using adenovirus vector injected into the hindlimb muscles was performed for cardiac failure of UM-X 7.1 hamster, a model of dilated cardiomyopathy.
1. In this model, serum sfas level 4 weeks after gene therapy was markedly increased in the sFas gene therapy group, compared to the control group with Lac Z gene (500mg/ml vs 0 of control).
2. However, survival rate 5 and 10 weeks later was similar between the sFas gene therapy group (71% and 50%) and the Lac Z control group (72% and 48%).
3. There was no significant difference of LV endodiastolic dimension, ejection fraction, and endodiastolic pressure 10 weeks after gene therapy. Also, heart weight, the extent of fibrosis, the % of TUNEL-positive cardiomyocytes, and the transverse size of cardiomyocytes did not show significant differences between the two groups.
In conclusion, sFas gene therapy does not inhibit the progression of cardiac failure in UM-X 7.1 hamster, in spite of marked increase of serum sFas. This suggests that Fas-Fas ligand system is independent of the progression of dilated cardiomyopathy of UM-X 7.1 hamster.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Watanabe, Motohiro: "Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy"Annals of Nuclear Medicine. 15. 13-19 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takemura, Genzou: "Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes"Journal of Pathology. 193. 546-556 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki, Masanori: "Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesion using ultrasound integrated backscatter. Comparison between histology and integrated backscatter images"Journal of the American College of Cardiology. 38. 486-492 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki, Masanori: "In Vivo Quantitative Tissue Characterization of Human Coronary Arterial Plaques Using Integrated Backscatter Intravascular Ultrasound and Comparison with Angioscopic findings"Circulation. 105. 2487-2492 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Motohiro Watanabe, Kohshi Gotoh, Kenshi Nagashima, Yoshihiro Uno, Toshiyuki Noda, Kazuhiko Nishigaki, Genzou Takemura, Motoo Kanoh, Norio Yasuda, Yasushi Ohno, Shinya Minatoguchi, Hisayoshi Fujiwara: "Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy"Annals of Nuclear Medicine. 15(1). 13-19 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Genzou Takemura, Sathoshi Kato, Takuma Aoyama, Yukihiro Hayakawa, Motoo Kanoh, Rumi Maruyama, Masazumi Arai, Kazuhiko Nishigaki, Shinya Minatoguchi, Kazunori Fukuda, Takako Fujiwara, Hisayoshi Fujiwara: "Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes"Journal of Pathology. 193. 546-556 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masanori Kawasaki, Hisato Takatsu, Toshiyuki Noda, Yoko Ito, Akihisa Kunishima, Masazumi Arai, Kazuhiko Nishigaki, Genzou Takemura, Norihiko Morita, Shinya Minatoguchi, Hisayoshi Fujiwara: "Noninvasive quantitative tissue characterization and two-dimensional colorcoded map of human atherosclerotic lesion using ultrasound integrated backscatter. Comparison between histology and integrated backscatter images"Journal of the American College of Cardiology. 38(2). 486-492 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masanori Kawasaki, Hisato Takatsu, Toshiyuki Noda, Keiji Sano, Yoko Ito, Kenji Hayakawa, Kunihiko Tsuchiya, Masazumi Arai, Kazuhiko Nishigaki, Genzou Takemura, Shinya Minatoguchi, Takako Fujiwara, Hisayoshi Fujiwara: "In Vivo Quantitative Tissue Characterization of Human Coronary Arterial Plaques Using Integrated Backscatter Intravascular Ultrasound and Comparison with Angioscopic findings"Circulation. 105. 2487-2492 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki, Masanori: "In Vivo Quantitative Tissue Characterization of Human Coronary Arterial Plaques Using Integrated Backscatter Intravascular Ultrasound and Comparison with Angioscopic findings"Circulation. 105. 2487-2492 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe, Motohiro: "Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy"Annals of Nuclear Medicine. 15. 13-19 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takemura, Genzou: "Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes"Journal of Pathology. 193. 546-556 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki, Masanori: "Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesion using ultrasound integrated backscatter. Comparison between histology and integrated backscatter images"Journal of the American College of Cardiology. 38. 486-492 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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