Soluble Fas, an inhibitor of apoptosis, gene therapy using adenovirus vector for ischemia-reperfusion injury

• Project/Area Number: 13670699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: GIFU UNIVERSITY
• Principal Investigator: MINATOGUCHI Shinya Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (20190697)
• Co-Investigator(Kenkyū-buntansha): FUJIWARA Hisayoshi Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (80115930) ; KOSAI Kenichiro School of Medicine, Assosiate Professor, 医学部, 助教授 (90258418)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: sFas gene therapy / myocardial infarction / LV remodeling / heart failure / Fas / Fas Ligand system / Fasリガンド・システム

Research Abstract

We examined potential therapeutic effects of soluble Fas (sFas), an inhibitor of apoptosis, on post-infarct left ventricular remodeling and heart failure. On the 3rd day of myocardial infarction (MI) of mice, adenovirus encoding sFas (Ad.CAG-sFas) was injected into the hindlimb muscle (1x10^9 pfu/mouse) to deliver sFas gene. As a control, adenovirus encoding LacZ gene was used. The treatment with sFas gene successfully suppressed apoptosis of granulation tissue cells, resulting in "a cell-rich scar tissue" at chronic stage (4 weeks later) in which blood vessels and myofibroblasts were abundant among fibrous tissue. The treatment greatly alleviated post-infarct left ventricular remodeling (based on improved echocardiogram and reduced heart to body weight ratio) and dysfunction (based on hemodynamic measurements). The results may imply a new therapeutic strategy against post-infarct heart failure, which is applicable even at subacute stage of MI.

Research Products

• [Publications] Minatoguchi S et al.: "Crosstalk among noradrenaline, adenosine and protein kinase C in the mechanisms of ischemic preconditioning"J Cardiovasc Pharmacol. 41(Suppl.1). S39-S47 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hayakawa K et al.: "Sensitivity to apoptosis signal, clearance rate, and ultrastructure of fas ligand-induced apoptosis in in vivo adult cardiac cells"Circulation. 105. 3039-3045 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawasaki M et al.: "Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesion using ultrasound integrated backscatter. Comparoson between histology and integrated backcatter images"Journal of the American College of Carsiology. 38(2). 486-492 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawasaki M et al.: "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
• [Publications] Shinya Minatoguchi, Yoshihiro Uno, Tatsuya Kariya, Masazumi Arai, Ningyuan Wang, Kazuaki Hashimoto, Yoshio Nishida, Rumi Maruyama, Genzou Takemura, Takako Fujiwara, Hisayoshi Fujiwara: "Crosstalk among noradrenaline, adenosine and protein kinase C in the mechanisms of ischemic preconditioning"J Cradiovasc Pharmacol. 41(Suppl. 1). S39-S47 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hayakawa K, Takemura G, Koda M, Kawase Y, Maruyama R, Li Y, Minatoguchi S, Fujiwara T, Fujiwara H.: "Sensitivity to apoptosis signal, clearance rate, and ultrastructure of fas ligand-induced apoptosis in vivo adult cardiac cells"Circulation. 105. 3039-45 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [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 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(2). 486-492 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [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