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Molecular mechanisms of smooth muscle proliferation after arterial injury and prevention using gene therapies

Research Project

Project/Area Number 14570644
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SUZUKI Jun-ichi (2003)  Tokyo Medical and Dental University, Cardiovascular Medicine, Junior Lecturer, 医学部附属病院, 助手 (90313858)

角田 恒和 (2002)  東京医科歯科大学, 医学部附属病院, 助手 (30262190)

Co-Investigator(Kenkyū-buntansha) AMANO Jun  Shinshu University, Department of Surgery, Professor, 医学部外科学, 教授 (20138283)
ISOBE Mitsuaki  Tokyo Medical and Dental University, Cardiovascular Medicine, Professor, 大学院・医歯学総合研究科, 教授 (80176263)
鈴木 淳一  東京医科歯科大学, 医学部附属病院, 助手 (90313858)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsinflammation / gene therapy / nuclear factor-kappa B / smooth muscle / coronary intervention / restenosis / 細胞接着分子 / 中和抗体 / 臨床応用 / 動脈硬化 / 平滑筋 / 副刺激 / T細胞 / ノックアウトマウス / セレクチン / 接着分子 / NFκB
Research Abstract

Background. The major disadvantage of the use of percutaneous coronary intervention (PCI) is the frequent occurrence of restenosis after an initially successful procedure; inflammation is a central event in this progression. Methods and Results. To evaluate the effectiveness of blocking inflammation to prevent neointimal formation, we made several murine and rat arterial remodeling models. We showed that anti-VCAM-1 antibody prevented arterial neointimal formation after arterial injury in a murine model. TNF receptor deficiency in donor organs suppressed coronary arterial neointimal formation in a murine heart transplant model. Anti-ICOS antibody suppressed inflammation in a myocarditis model or a transplantation model. An anti-selectin compound also showed suppressed ischemia reperfusion injury in rats. We performed several gene therapies to prevent arterial remodeling. Antisense Egr-1 or anti-MMP-2 ribozyme transfection prevented neointimal formation in murine cardiac transplantation models. Based on these results, we performed clinical trials to prevent restenosis after PCI. The initial case was suffering from effort angina with stenosis in the proximal and middle portions of the right coronary artery. The patient received two stents; we delivered the NF-kB decoy at the distal site and no decoy at the proximal site. Six months after the PCI, the NF-kB decoy suppressed restenosis compared to no decoy transfection. Condusion. Inflammation plays a pivotal role in arterial remodeling. These results suggest the clinical usefulness of gene transfection after PCI.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Suzuki J.: "Tumor necrosis factor receptor-1 and -2 double deficiency reduces graft arterial disease in murine cardiac allografts."Am J Transplant.. 3. 968-976 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki J.: "Initial clinical cases using an NF-kB decoy at the site of the coronary stenting for prevention of restenosis."Circ J.. 68. 270-271 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki J.: "Anti-VCAM1 and anti-VLA4 monocolonal antibodies inhibit neointimal hyperplasia in the murine model of arterial injury."Acuta Cardiologica. 59. 147-152 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Futamatsu H.: "Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway."Cardiovasc Res.. 59. 95-104 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kosuge H.: "The induction of immunological tolerance to cardiac allograft by simultaneous blockade of ICOS and CTLA4 pathway."Transplantation. 75. 1374-1379 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onai Y.: "Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion inujury."Eur J Pharm.. 481. 217-225 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Stizuki J.: "Tumor necrosis factor receptor -1 and -2 double deficiency reduces graft arterial disease in murine cardiac allografts."Am J Transplant.. 3. 968-976 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki J.: "Initial clinical cases using an NF-kB decoy at the site of the coronary stenting for prevention of restenosis."Circ J.. 68. 270-271 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki J.: "Anti-vascular cell adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies inhibit neointrmal hyperplasia in the murine model of arterial injury."Acuta Cardiologica. 59. 147-152 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Futamatsu H.: "Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway."Cardiovasc Res.. 59. 95-104 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kosuge H.: "The induction of immunological tolerance to cardiac allograft by simultaneous blockade of inducible co-stimulator (ICOS) and CTLA4 pathway."Transplantation.. 75. 1374-1379 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onai Y.: "Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia / reperfusion injury."Eur J Pharm.. 481. 217-215 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onai Y.: "Inhibition of 1kB phosphorylation in cardiomyocytes attenuates myocardial ischemia / reperfusion injury."Cardiovasc Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukioka K.: "Expression of matrix metalloproteinases in cardiac allograft vasculopathy and its attenuation by anti MMP-2 ribozyme gene transfection."Cardiovasc Res.. 56. 472-478 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada Y.: "Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen."J Surg Res.. 115. 294-302 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jun-ichi Suzuki: "Anti-vascular cell adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies inhibit neointimal hyperplasia in the murine model of arterial injury"Acta Cardiologica. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jun-ichi Suzuki: "Initial clinical cases using an NF-kB decoy at the site of the coronary stenting for prevention of restenosis"Circulation Journal. 68. 270-271 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jun-ichi Suzuki: "Tumor necrosis factor receptor -1 and -2 double deficiency reduces graft arterial disease in murine cardiac allografts"American Journal of Transplantation. 3. 968-976 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hisanori Kosuge: "The induction of immunological tolerance to cardiac allograft by simultaneous blockade of inducible co-stimular (ICOS) and CTLA4 pathway"Transplantation. 75. 1374-1379 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuko Wada: "Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen"Journal of Surgical Research. 115. 294-302 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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