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2001 Fiscal Year Final Research Report Summary

Gene therapy of advanced heart failure

Research Project

Project/Area Number 10307017
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

TOYO-OKA Teruhiko  University Tokyo, Health Service Center, Professor, 保健管理センター, 教授 (00146151)

Co-Investigator(Kenkyū-buntansha) SHIN Wee soo  University Tokyo, Health Service Center, Research Associate, 保健管理センター, 助手 (10211971)
SUZUKI Jun-ichi  University Tokyo, Health Service Center, Assistant Professor, 保健管理センター, 講師 (50260485)
UEHARA Yoshio  University Tokyo, Health Service Center, Associate Professor, 保健管理センター, 助教授 (40184965)
KAWADA Tomie  Niigata University, Hospital Division of Pharmacy, Associate Professor, 病院, 薬剤部・現助教授 (00186107)
Project Period (FY) 1998 – 2000
KeywordsGene / Therapy / rAAV / δ-SG / Lac Z / CMV / Echocardiography
Research Abstract

The efficacy of gene therapy of advanced heart failure should be examined by the in vivo contractility of cardiac muscle and the prognosis of the experimental animals. We prepared normal δ-SG gene or reporter gene (Lac Z), driven by the same CMV promoter and administered intramuscularly to DCM hamster hearts (TO-2 strain) under open-chest surgery. In a preliminary study, we examined the appropriate age of the animals just before the onset of myocardial degeneration (Kawada et al., B.B.R.C., 2001).
The life-span of normal hamsters is 100week, and TO-2 strain hamsters survive up to 30 weeks (Sole, Hamster Information Srvice 1986). In TO-2 animals, the group administered Lac Z alone strated to die from 4 weeks old and sharply declined to die around 160 days. These periods matched to the data reported previously. In contrast, another group cotransfected δ-SG and Lac Z did not die and remained active to 250 day old. The echocardiography confirmed the improved LVDs, %FS, LVEF but not LVDd. Thus this is the first report that the grave prognosis of advanced failure was rescued by the gene therapy (Kawada et al., Proc.Natl. Acad. Sci. USA, 2002).

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Shin WS, Tanaka M, Suzuki J, Toyo-ok T.: "A homoplamic mitochondrial DNA mutation with characteristic D-loop sequence as a risk factor cardioselective expression of mypoathy"Am. J. Hum. Gen.. 67. 1617-1620 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Xi H, Shin WS, Suzuki J. et al.: "Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol"J. Cardiovasc, Pharmacol.. 36(Suppl.2). S25-S29 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang Y, Chen J, Wang Y, et al.: "Crucial role of type 1, but not type 3, inositol 1,4,5-trisphoshpate IP_3 receptors in IP_3-induced Ca^<2+> release, capacitative Ca^<2+> entry, and proliferation of A7r5 vascular smooth muscle cells"Circ. Res.. 88. 202-209 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawada T, Sakamoto A, Nakazawa M, et al.: "Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy"Biochem. Biophys. Res. Commun.. 284. 435 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toyo-oka T.: "Long-and short-term cross talk between endothelial cells and vascular smooth muscle cells mediated by nitric oxide"Jpn. Heart J. 2001. (In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawada T, Nakazawa M, Sakamoto A, et al.: "Long-term rescue of hereditrary form of dilated cardiomyopathy by rAAV vector-mediated somatic gene therapy"Proc. Natl. Acad. Sci., USA. 99. 901-906 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin WS, Toyo-oka T.: "Coculture of endothelial cells and vascular smooth muscle cells."Humana Press (London).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin W.S., Tanaka M., Suzuki J., Toyo-oka T.: "A homoplamic mitochondrial DNA mutation with characteristic D-loop sequence as a risk factor cardioselective expression of myopathy"Am. J. Hum. Gen.. 67. 1617-1620 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xi H., Shin W.S., Suzuki J. et al.: "Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol"J. Cardiovasc. Pharmacol. 36 (Suppl. 2). S25-S29 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang Y., Chen J., Wang Y., et al.: "Crucial role of type 1, but not type 3, inositol 1,4,5-trisphosphate IP_3 receptors in IP_3-induced Ca^<2+> release, capacitative Ca^<2+> entry, and proliferation of A7r5 vascular smooth muscle cells"Circ. Res.. 88. 202-209 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawada T., Sakamoto A., Nakazawa M. et al.: "Morpholpgical and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy"Biochem. Biophys. Res. Commun.. 284. 431-435 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toyo-oka T.: "Long- and sort-term cross talk between endothelial cells and vascular smooth muscle cells mediated by nitric oxide"Jpn. Heart J.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawada T., Nakazawa M., Sakamoto A., et al.: "Long-term rescue of hereditrary form of dilated cardiomyopathy by rAAV vector-mediated somatic gene therapy"Proc. Natl. Acad. Sci., USA. 99. 901-906 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin W.S. and Toyo-oka T.: "Conculture of endothelial cells and vascular smooth muscle cells"Humana Press (London).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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