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A novel gene therapy for congestive heart failure.

Research Project

Project/Area Number 08557079
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Thoracic surgery
Research InstitutionOsaka University

Principal Investigator

MATSUDA Hikaru  Osaka University Medical School, Professor, 医学部, 教授 (00028614)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasuhumi  Osaka University Institute for Molecular and Cellular Biology, Associate Profess, 細胞生体工学センター, 助教授 (10177537)
HIRATA Nobuaki  Osaka University Medical School, Assistant Professor, 医学部, 助手 (70283752)
SAWA Yoshiki  Osaka University Medical School, Assistant Professor, 医学部, 助手 (00243220)
OHTAKE Shigeaki  Osaka University Medical School, Instructor, 医学部, 講師
正井 崇史  大阪大学, 医学部, 助手 (30273650)
門場 啓司  大阪大学, 医学部, 講師 (00185886)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1996: ¥13,300,000 (Direct Cost: ¥13,300,000)
Keywordsin-vivo gene transfection / HVJ liposome method / beta 2 adrenergic receptor / B2Adrenerigic receptor / 心不全治療 / Beta2 Adrenergic Receptor
Research Abstract

Beta adrenergic receptor system has a major important role in cardiac contraction. If the receptor can be increased by exogenous administration in the hearts in which the receptor is downregulated, this approach may improve the cardiac function. To test whether in-vivo gene transfection of beta 2 adrenergic receptor (B2AR) into the normal and the failing heart by constriction of the abdominal aorta can enhance cardiac function, we transfected with cDNA of the receptor in the heart of Sprague-Dawley rat by intracoronary infusion of hemaagglutinating virus of Japan (HVJ) -liposome plasmid complex including human B2AR gene (BAR (+) and pBAR (+) group). Control hearts were infused with HVJ-liposome plasmid complex without the receptor gene (BAR (-) and pBAR (-) group). Four days after transfection, the hearts were examined. Immunohistochemical labeling using specific antibody to human B2AR demonstrated that the sarcolemma of the myocytes in BAR (+) and pBAR (+) groups was well labeled, while anywhere in BAR (-) and pBAR (-) groups was not. Ligand binding assay using [125I] -cyanopindolol revealed that the receptor density of the hearts in BAR (+) and pBAR (+) groups was significantly higher than in BAR (-) and pBAR (-) groups. Evaluation using Langendorff system demonstrated that developed pressure and maximum derivative of the left ventricle after infusion of isoproterenol were significantly higher in BAR (+) and pBAR (+) groups than in BAR(-) and pBAR (-) groups. Minimum derivative of the left ventricle after infusion of isoproterenol was significantly lower in BAR (+) and pBAR (+) groups than in BAR (-) and pBAR (-) groups. Our results indicated that beta 2 adrenergic receptor was overexpressed approximately 4 times in normal rat hearts and the failing heart by pressure overload by in-vivo gene transfection using HVJ liposome method and the transfected hearts demonstrated marked enhancements in cardiac response after infusion of isoproterenol.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Sawa Y,: "Efficient gene transfer method into the whole heart through the coronary artery with Hemaggulutinating virus of Japan liposome." J.Thorac.Cadiovasc.Surg.,. 113(3). 512-519 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki K,: "In vivo gene transfection with Heat Shock Protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat." J.Clin.Invest.,. 99(7). 1645-1650 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sawa Y,: "A novel strategy for myocardial protection using in vivo transfection of cis element ´decoy´ against NFkB binding site." Circulation,. 96(Suppl II). II-280-II-285 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sawa Y,Kaneda Y,Matsuda H,et al.: "Efficient gene transfer method into the whole heart through the coronary artery with Hemaggulutinating virus of Japan liposome." J.Thorac.Cardiovasc.Surg.113 (3). 512-519 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki K,Sawa Y,Kaneda Y,Matsuda H,at al.: "In vivo gene transfection with Heat Shock Protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat." J.Clin.Invest.99 (7). 1645-1650 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sawa Y,Kaneda Y,Matsuda H,et al.: "A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkB binding site." Circulation. 96 (Suppl II). 280-285 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sawa Y, Kaneda Y, Matsuda H, et al.: "Effcient gene transfer method into the whole heart through the coronary artery with Hemaggulutinating virus of Japan liposome." J.Thorac.Cardiovasc.Surg.,. 113(3). 512-519 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki K, Sawa Y, Kaneda Y, Matsuda H, et al..: "In vivo gene transfection with Heat Shock Protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat." J.Clin.Invest.,. 99(7). 1645-1650 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sawa Y, Kaneda Y, Matsuda H.et al..: "A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkB binding site." Circulation,. 96(Suppl II). II-280-II-285 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshiki Sawa: "Efficacy of in vivo gene transfection into transplanted rat heart by coronary infusion of HVJ liposome" Circulation.

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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