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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)
阪本 英二  国立循環器病センター, 研究所, 室長(研究職) (40291067)
石川 隆俊  東京大学, 大学院・医学系研究科, 教授 (30085633)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥29,600,000 (Direct Cost: ¥29,600,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1998: ¥15,000,000 (Direct Cost: ¥15,000,000)
KeywordsGene / Therapy / rAAV / δ-SG / Lac Z / CMV / Echocardiography / リポソーム / サイコグリカン
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).

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hikiji H et al.,: "Peroxynitrite production by TNF-α and IL-1β."Am.J.Physiol.. 278. E1031-E1037 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang YP et al.,: "Autocrine action and its underlying mechanism..."J.Biol.Chem.. 275. 28739-28749 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shin WS et al.,: "A homoplamic mitochondrial DNA mutation..."Am.J.Hum.Gen.. 67. 1617-1620 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xi H et al.,: "Dystrophin disruption might be related to......"J.Cardiovasc.Pharmacol.. 36. S25-S29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki J et al.,: "Screening and/or follow-up with........"Radiology. 6. 189-197 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang YP et al.,: "Crucial role of type 1, but not type 3,........."Circ.Res.. 88. 202-209 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki J, et al.: "Morphological onset and early diagnosis in apical hypertrophic cardiomyopathy ; a long-term analysis with nuclear magnetic resonance imaging"J. Am. Coll. Cardiol.. 33:. 146-151 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada T, et al.: "Precise identification of gene-products in hearts after in vivo gene transfection, using Sendai virus-coated proteoliposomes"Biochem. Biophys. Res. Commun.. 259. 408-413 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirawa N, et al.: "Long-term inhibition of renin-angiotensin system sustainains memory function in aged Dahl rats"Hypertension. 34:. 496-502 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Asano M, et al.: "Eicosapentaenoic acid inhibits vasopressin-activated Ca^<2+> influx and cell proliferation in rat aortic smooth muscle cell line"Eur. J. Pharmacol.. 379;. 199-209 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada T, et al.: "Strain-and age-dependent loss of sarcoglycan complex in cardiomyopathic hamster hearts and its reexpression by δ-sarcoglycan gene transfer in vivo"F. E. B. S. Lett.. 458;. 405-8, (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawaguchi H, et al.: "Apoptotic cell death in acute myocardial injury induced by isoproterenol is mediated by nitric oxide"J. Cardiovasc. Pharmacol.. 34(Suppl.4);. S25-8, (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagoshi H.et al.: "Prostaglandin D2 inhibits inducible nitric oxide synthaseexpression in rat vascular smooth muscle" Circ.Res.82. 204 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamazaki T.et al.: "Transient hypertension in male adolescents when measured by women" Heart. 79. 104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimamoto R.et al.: "Measuring the diameter of coronary artenes on MR angiograms using spatia profile curves" Am.J.Roent.170. 889-893 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uehara H.et al.: "A hypertensive father,but not hypertensive mother,determines blood pressure in normotensive male offspring through body mass index" J Human Hyperten.12. 441-445 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki J.et al.: "Morphological onset and early diagnosis inapical hypertrophic cardiomyopathy" J Am Coll Cardiol. 33. 146-151 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawada T.et al.: "In vivo Gene Supplementation for the Therapy of Cardimyopathy" J Card Failure. In press.

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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