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Gene Therapy in the Cardiovascular Disease

Research Project

Project/Area Number 09044299
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

OGIHARA Toshio  Osaka University Faculty of Medicine, Professor, 医学部, 教授 (60107042)

Co-Investigator(Kenkyū-buntansha) DZAU Victor J  Harvard University Faculty of Medicine, Professor, 医学部, 教授
MORISHITA Ryuichi  Osaka University Faculty of Medicine, Associate Professor, 医学部, 助教授 (40291439)
MORIGUCHI Atushi  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (10273666)
KANEDA Yasufumi  Osaka University Faculty of Medicine, Professor, 医学部, 教授 (10177537)
HIGAKI Jituo  Osaka University Faculty of Medicine, Associate Professor, 医学部, 助教授 (70189744)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsgene therapy / HGF / decoy / restenosis / peripheral arterial disease / アンチセンス / ベクター
Research Abstract

Recently, gene therapy has been center of interests in the treatment of cardiovascular disease. One of major targets for gene therapy is restenosis after angioplasty. To achieve the complete inhibition of neointimal formation, we have identified cell cycle regulatory proteins as a target. Application of decoy strategy to regulate the transcription of disease-related genes has important therapeutic potentials. Thus, decoy against transcription factor E2F that is essential for cell proliferation resulted in the complete inhibition of neointimal formation up to 8 weeks after transfection. We also employed porcine coronary artery balloon injury model. Transfection of E2F decoy ODN using hydrogel catheter resulted in a significant inhibition of neointimal formation. Currently, we plan to start human gene therapy trial using E2F decoy to treat restenosis after angioplasty.
Alternatively, we also focused on the therapeutic angiogenesis strategy using human hepatocyte growth factor (HGF) gene. Number of vessels in rat hindlimb transfected with HGF gene was significantly. increased, accompanied by a significant increase in blood flow. Thus, we provided direct in vivo evidence for angiogenesis induced by HGF gene in rat ischemic hindlimb model. Based upon these findings, we submitted the clinical protocol of human gene therapy using HGE to treat peripheral arterial disease to Osaka University.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Yamada K. Moriguchi A.: "Efficient oligonucleotides delivery using HVJ-liposome method in the central nervous system" Hypertension. 28. 409-413 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hayashi S., Morishita R.: "In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid" Gene Therapy. 3. 878-885 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R., Gibbons G.H.: "Molecular delivery system for antisense olgonucleotides ; enhanced effectiveness of antisense oligonucleotides by HVJ-liposome mediated transfer" Journal of Cardiovascular Pharmacology & Therapeutics. 2. 213-222 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki M., Morishita R.: "Survival of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and β-galactosidase gene in non-infarcted area, but not myocardial infarcted area" Gene Therapy. 4. 120-127 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki M., Morishita R.: "Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ (Hemagglutinating Virus of Japan) liposome method" J Mol Cell Cardiol. 29. 949-959 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R., Sugimoto T.: "In vivo transfection of cis element “decoy" against NFKB binding site prevented myocardial infarction as gene therapy" Nature Medicine. 3. 894-899 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R., Aoki M.: "Kluwer Academic publisyers" Gene therapy for myocardial infarction, 531-550 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R., Aoki M.: "Kluwer Academic Publishers" Function analysis of tissue renin-angiotensin System using “Gain and Loss of Function" Approaches ; In vivo test of in vitro hypothesis. in “Angiotensin II receptor blockade ; physiological, in press (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada K,Moriguchi A,Morishita R,Aoki M,Nakamura Y,Mikami H,Oshima T,Ninomiya M,Kaneda Y,Higaki J,Ogihara T.: "Efficient oligonucleotides delivery using HVJ-liposome method in the central nervous system." Hypertension. 28. 409-413 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hayashi S,Morishita R,Aoki M,Moriguchi A,Kida I,Nakajima M,Kaneda Y,Higaki J,Ogihara T.: "In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid." Gene Therapy. 3. 878-885 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R,Gibbos GH,Horiuchi M,Nakajima M,Ellison KE,Lee W,Kaneda Y,Ogihara T,Dzau VJ.: "Molecular delivery system for antisense olgonucleotides : enhanced effectiveness of antisense oligonucleotides by HVJ-liposome mediated transfer." Journal of Cardiovascular Pharmacology & Therapeutics. 2. 213-222 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki M,Morishita R,Higaki J,Moriguchi A,Hayashi S,Matsushita H,Kida I,Tomita N,Sawa Y,Kaneda Y,Ogihara T.: "Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and beta-galactosidase gene in non-infarcted area, but not myocardial infarcted area." Gene Therapy. 4. 120-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki M,Morishita R,Muraishi A,Moriguchi A,Sugimoto T,Maeda K,Dzau VJ,Kaneda Y,Higaki J,Ogihara T.: "Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ (Henagglutinating Virus of Japan )-liposome method." J Mol Cell Cardiol. 29. 949-959 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R,Sugimoto T,Aoki M,Kida I,Tomita N,Moriguchi A,Maeda K,Sawa Y,Kaneda Y,Higaki J,Ogihara T.: "In vivo transfection of cis element "decoy"against NFkB binding site prevente myocardial infarction as gene therapy." Nature Medicine. 3. 894-899 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki J,Isobe M,Morishita R,Aoki M,Horie S,Okubo Y,Kaneda Y,Sawa Y,Matsuda H,Ogihara T,Sekiguchi M.: "Prevention of graft coronary arteriosclerosis by antisense cdk 2 kinase oligonucleotide." Nature Medicine. 3. 900-903 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R,Gibbons GH,Horiuchi M,Kaneda Y,Ogihara T,Dzau VJ.: "Role of AP-1 complex in angiotensin II-mediated transforming growth factor-beta expression and growth of smooth muscle cells : using decoy approach against AP-1 binding site." Biochemical Biophysics Research Communication. 243. 361-367 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R,Higaki J,Tomita N,Ogihara T.: "Application of transcription factor "decoy"strategy as means of gene therapy and study of gene expression in cardiovascular disease." Circulation Reserch. 82. 1023-1028 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R,Yamada S,Yamamoto K,Tomita N,Kida I,Sakurabayashi I,Kikuchi A,Kaneda Y,Lawn R,Higaki J,Ogihara T.: "Novel therapeutic strategy for atherosclerosis : ribozyme oligonucleotides against apolipoprotein (a) selectively inhibit apolipoprotein (a) , but not plasminogen, gene expression." Circulation. 98. 1898-1904 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawamura I,Morishita R,Tomita N,Elizabeth L,Aketa M,Tsujimoto S,Manda T,Tomoi M,Kida I,Higakai J,Kaneda Y,Ogihara T.: "Intratumoral injection of oligonucleotides to the NFkB binding site inhibits cachexia in a mouse tumor model." Gene Therapy. 6. 91-97 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morishita R, Gibbons GH: "Role of Ao-1 complex in angiotensin II-mediated transforming growth factor-β expression and growth of smooth muscle cells using decoy anginst AP-1 binding site" Biochemicak Biophysics Research Communication. 243. 361-367 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R, Ogihara T: "In vivo evaluation of in vivo hypothesis using “gain or loss" of functional analysis of renin-angiotensin system" American Journal of Hyperrension. 11. 507-513 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R, Higaki J: "Application of transcription factor “decoy" strategy as means of gene therapy and study of gene expression in cardiovascullar disease" Ciroulation Research. 82. 1023-1028 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakano N, Morishita R: "Negative regulation of local hepatocyte growth factor (HGF)expression by angiotensin II and transforming growth factor :; in blood vessel ; petental role of HGF in cardiovascullar disease" Hypertension. 32. 444-451 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R, Yamada S: "Novel therapeutic strapeutic sor atherosclerosis ; ribozyme oligonucleotides against apolipoprotein(a)selectively inhibit apolipoproteing(a), but not plasminigen,gene expression." Circulation. 98. 1898-1904 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamura I, Morishita R: "Intratumoral injection of oligonucleotides to the NFkB binding site inhibits cachexia in a mouse tumor model" Gene Therapy. 6. 91-97 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R, Aoki M: "Kluwer Academic Publishers" Gene therapy for myocardial infarction., 531-550 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R, Aoki M: "Kluwer Academic Publishers(in press)" Function analysis of tissue renin-angiotensin System Unig “Gain and Loss of Function" Approaches : In vivo test of physiological in vivo hypothesis, in Angiotensin II reeoptor blockade : and clinical implication, (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R: "Molecular delivery system for antisense olgonucleotides:enhanced effectiveness of antisense oligonucleotides by HVJ-liposome mediated transf" Journal of Cardiovascular Pharmacology & Therapeutics. 2. 213-222 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aoki M: "Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ(Hemagglutinating Virus of Japan)-liposome method." Journal of Molecular and Cellular Cardiology. 29. 949-959 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "In Vivo Transfection of cis element "decoy" against NFkB binding site prevented myocardial infarction as gone therapy." Nature Medicine. 3. 894-899 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki J: "Prevention of graft coronary arteriosclerosis by antisense cdk 2 kinase oligonucleotide." Nature Medicine. 3. 900-903 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sawa Y: "A novel strategy for myocardial protection using in vivo transfection of cis element "decoy" against NFkB binding site:evidence for a role of NFkB in ischemic-reperfus injury." Circulation. 96. 280-285 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "Role of AP-1 complex in angiotensin II-mediated transforming growth factor-β expression and growth of smooth muscles cells:using decoy approach against AP-1 binding site" Biochemical Biophysics Research Communication. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "Ischemic Heart" Kluwer Academic Publishers (in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "Angiotensin II receptor blockade:physiological and clinical implications" Kluwer Academic Pub (in press), (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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