• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Application of In vivo Gene Transfer for the Analysis of Pathophysiology and Treatment in the Cardiovascular Disease

Research Project

Project/Area Number 11470163
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

MORISHITA Ryuichi  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40291439)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasufumi  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (10177537)
HIGAKI Jitsuo  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70189744)
守口 篤  大阪大学, 医学系研究科, 助手 (10273666)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsgene therapy / angiogenesis / ASO / HGF / CAP / endotlelial cells / ASO / 再狭 / NFkB / 核酸医薬 / E2F / 閉塞性動脈硬化症 / 心筋梗塞
Research Abstract

Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as peripheral arterial disease, restenosis after angioplasty, vascular bypass graft occlusion, transplant coronary vasculopathy, myocardial infarction, for which no known effective therapy exists. Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia and myocardial ischemia. Thus, the strategy for therapeutic angiogenesis using angipgenic growth factors should be considered for the treatment of patients with critical limb ischemia or myocardial infarction. From this viewpoint, we focused on a novel angiogenic growth factor, HGF (hepatocyte growth factor). Although HGF is originally identified as a most potent mitogen for hepatocytes, we found the potent angiogenic property of HGF in rabbit hindlimb model. Accordingly, we planed human clinical trial using intramuscularl … More y injection of naked human HGF plasmid (0.5mg x 4) two times. Currently, HGF gene transfer was performed in 6 patients with PAD (n=3) or Buerger (n=3) graded by Fontaine III or IV who had failed conventional therapy. Reduction of pain scale (>1cm in visual analog scale) was observed in 5 of 6 patients (efficacy rate is 83%). Increase in ABI (Ankle Pressure Index) >0.1 was observed in 5 of 5 patients (efficacy rate is 100%), while 1 patients failed to measure API from before gene therapy due to strong calcification. In addition, TPI (Toe pressure Index) was also Increased in 2 of 2 patients (efficacy rate is 100%), whereas other 3 patients failed to measure TPI from before gene therapy due to ischemic ulcer. Currently, severe adverse effects could not be detected in all patients. Although the present data are still preliminary, the initial clinical outcome with naked HGF plasmid DNA transfer seems to be useful as sole therapy for PAD. In addition, we proved the potent angiogenic activity of HGF in the stimulation of collateral formation in myocardium. Based upon these findings, we submitted human clinical trial using HGF to treat chronic heart failure. Less

Report

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

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angioge nesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease"Gene Therapy. 8. 181-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T, Sakai N: "Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons"Gene Therapy. 8. 1167-1173 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Morishita R, Hiraoka K, Aoki M, Nakagami H, Yamasaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes"Circulation. 104. 2344-2350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura S, Morishita R, Hayashi K, Yamamoto K, Nakagami H, Kaneda Y, Sakai N, Ogihara T: "Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element 'decoy' of nuclear factor-kB binding site as a novel molecular strategy"Gene Therapy. 8. 1635-1642 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N, Aoki M, Ogihara T, Yasufumi K, Morishita R: "Local delivery of plasmid DNA into rat carotid artery using ultrasound"Circulation. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura T, Morishita R, Asai T, Tsuboniwa N, Aoki M, Sakonjo H, Yamasaki K, Hashiya N, Kaneda Y, Ogihara T: "Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model"Gene Therapy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Morishita R, Aoki M, Hashiya N, Yamasaki K, Makino H, Wakayama K, Azuma J, Ogihara T: Gene Therapy & Regulation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hind limb ischemia module: preclintcal study of treatment of peripheral arterial disease"Gene Therapy. (8). 181-189 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, Nakamura T, Kaneda Y, Sakai N: "Gene therapy for preventing neuronal death using hepatocyte growth factor in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CAI neurons"Gene Therapy. (8). 1167-1173 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Morishita R, Hiraoka K, Aoki M, Nakagami H, Yamasaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischernia module: molecular of delayed angiogenesis in diabetes"Circulation. (104). 2344-2350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura Y, Morishita R, Hayashi K, Yamamoto K, Nakagami H, Kaneda Y, Sakai N, Ogihara T: "Inhibition of intimal hyperplasic after balloon injury in rat carotid artery model using cis-elememt "decoy" of nuclear factor-kB binding afte a novel molecular strategy"Gene therapy. (8). 1635-1642 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N, Aoki M, Ogihara T, Kaneda Y, Morishita R: "Local delivery of plasmid DNA into rat carotid artery using ultrasound"Circulation. (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] Nakamura T, Morishita R, Asai T, Tsuboniwa N, Aoki M, Sakonjo H, Yamasaki K, Hashiya N, Kaneda Y, Ogihara T: "Molecular strategy using cis-element "decoy" of E2F binding alto inhibits neointimal formation in porcine balloon-injured coronary asiesy model."Gene Therapy. (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] Morishita R, Aoki M, Hashiya N, Yamasaki K, Makino H, Wakayama K, Azuma J, Ogihara T: Gene Therapy & Regulation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic anglogenesis Induced by human hepatocyte growth factor gene in rat and rabbit hind limb ischemfa models: preclinical study for treatment of pertphera1 arterial disease"Gene Therapy. 8. 181-189 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T, Sakai N: "Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons"Gene Therapy. 8. 1167-1173 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniyama Y, Morishita R, Hiraoka K, Aoki M, Nakagami H, Yamasaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes"Circulation. 104. 2344-2350 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimura S, Morishita R, Hayashi K, Yamamoto K, Nakagami H, Kaneda Y, Sakai N, Ogihara T: "Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element "decoy" of unclear factor-kB binding site as a novel molecular strategy"Gene Therapy. 8. 1635-1642 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N, Aoki M, Ogihara T, Kaneda Y, Morishita R: "Local delivery of plasmid DNA into rat carotid artery using ultrasound"Circulation. (in press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura T, Morishita R, Asai T, Tsuboniwa N, Aoki M, Sakonjo H, Yamasaki K, Hashiya N, Kaneda Y, Ogihara T: "Molecular strategy using cis-element "decoy" of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model"Gene Therapy. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Morishita R, Aoki M, Hashiya N, Yamasaki K, Makino H, Wakayama K, Azuma J, Ogihara T: "Gene Therapy & Regulation"(in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Aoki M,Morishita R,Taniyama Y,Kida I,Moriguchi A,Matsumoto K,Nakamura T,Kaneda Y,Higaki J,Ogihara T.: "Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium : up-regulation of essential transcription factor for angiogenesis,ets."Gene Therapy. 7. 417-427 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsushita H,Morishita R,Aoki M,Tomita N,Taniyama Y,Nakagami H,Shimozato T,Higaki J,Kaneda Y,Ogihara T.: "Transfection of antisense p53 tumor suppressor gene oligodeoxynucleotides into rat carotid artery resulted in abnormal growth of vascular smooth muscle cells."Circulation. 101. 1447-1452 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsushita H,Morishita R,Nata T,Aoki M,Nakagami H,Taniyama Y,Yamamoto K,Higaki J,Kaneda Y,Ogihara T.: "Hypoxis induced endothelial apoptosis through NFkB-mediated bcl-2 suppression : in vivo evidence of importance of NFkB in endothelial cell regulation."Circulation Research. 86. 974-981 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomita N,Morishita R,Lan HY,Yamamoto K,Hashizume M,Notakae M,Toyosawa K.Fulitani B,Mu W,Nikolic-Paterson DJ,Atkins RC,Kaneda Y,Higaki J,Ogihara T.: "In vivo administration of a nlenr transcription factor-kappaB decoy suppresses experimental crescentic glomcrulonophritis."Journal of American Society of Nephrology. 11. 1244-1252 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto K,Morishita R,Tomita N,Shimozato T,Nakagami H,Kikuchi A,Aoki M,Higaki J,Kaneda Y,Ogihara T.: "Ribozyme oligonucleotides against transforming growth factor-β inhibited neointimal formation after vascular injury in rat model : potentisl application of ribozyme strategy to treat cardiovascular diseage."Circulation. 102. 1308-1314 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi K,Nakamura S,Morishita R,Moriguchi A,Aoki M,Matsumoto K,Nakamura T,Kaneda Y,Sakai N,Ogihara T.: "In vivo transfer of human hepatocyte growth factor gene accelcrates re-endothelialization and inhibits neointimal formation after balloon injury in rat model."Gene Therapy. 7. 1664-1671 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morishita R,Aoki M,Nakamura S,Higaki J,Kaneda Y,Ogihara T.: "Gene therapy for cardiovascular disease using hepatocyte growth factor.Atherosclerosis V.The Fifth Saratoga International Conference."Edited by Numano F & Gimbrone MA.Ann New York Acad. 369-376 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaneda Y,Nakasima H,Tsuboniwa N,Morishita R.: "Progress of fusigenic viral-liposomes.Progress in Gene Therapy : basic and clinical frontiers."edited by Bertolottis R et al.VSP,. 225-243 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamura I, Morishita R, Tomita N, Aketa M, Tsujimoto S, Manda T, Tomoi M, Kida I, Hifakai J, Kaneda Y, Shimomura K, Ogihara T.: "Intratumoral injection of oligonucleotides to the NFkB binding site inhibits cachexia in a mouse tumor model"Gene Therapy. 6. 91-97 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi H, Oakamoto E, Fujimoto J, Ueki T, Kaneda Y, Tsutusi H, Nakanishi K,Sawa Y, Morishita R, Matusmoto K, Nakamura T,: "Curative gene therapy of liver cirrhosis by hepatocyte growth factor in rats"Nature Medicine. 5. 226-230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Nakamura S, Hayashi S, Taniyama Y, Moriguchi A, Nagano T, Taiji M, Noguchi H, Takeshita S, Matsumoto K, Nakamura T, Higaki J, Ogihara T.: "Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as "cytokine supplement therapy""Hypertension. 33. 1379-1384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi S, Morishita R, Nakamura S, Yamamoto K, Moriguchi A, Nagano T, Taizi M, Noguchi H, Matsumoto K, Nakamura T, Higaki J, Ogihara T.: "Potential role of hepatocyte growth factor,a novel angiogenic growth factor, in peripheral arterial disease : down-regulation of HGF in response to hypoxia in vascular in vascular cells"Circulation. 100. II301-II308 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Gibbons GH, Tomita N, Zhang L, Kaneda Y, Ohihara T, Dzau VJ.: "Anitisense oligodeozynucleotide inhibition of vascular angiotensin converting enzyme expression attenuates neointimal formation : evidence for tissue ACE function"Arteriosclerosis,Thrombosis & Vascular Biology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomika N, Morishita R, Lan HY, Yamamoto K, Hashizume M, Notakae M, Toyosawa K, Fujitani B,Mu W, Nikolic-Paterson DJ, Atkins RC, Kaneda Y, Higaki J, Ogihara T.: "In vivo administration of a clear transcription factor-kappaB decoy suppresses experimental crescentic glomerulonephritis"Journal of American Society of Nephrology. (in press).

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi