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Therapy for ischemic vascular diseases using soluble TNF-alpha receptor 1 gene

Research Project

Project/Area Number 14570671
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SUGANO Masahiro  Kyushu University, Medical Institute of Bioregulation, Assistant Professor, 生体防御医学研究所, 助教授 (20206395)

Co-Investigator(Kenkyū-buntansha) 門上 俊明  九州大学, 生体防御医学研究所, 助手 (40335980)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsmyocardial infarction / TNF-alpha / soluble TNF-alpha receptor 1 / angiogenesis / gene therapy / soluble TNF-alpha receptor
Research Abstract

Apoptosis is the major independent form of cardiomyocyte cell death in acute myocardial infarction (AMI). TNF-alpha release early in the course of AMI contributes to myocardial injury and TNF-alpha induces apoptosis in cardiomyocytes. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNER1 and an antagonist to TNF-alpha. Treatment with sTNFR1plasmid reduced the TNF-alpha bioactivity in the myocardium and the apoptosis of cardiomyocytes. As a result, the sTNFR1 plasmid significantly reduced the area of myocardial infarction at 2 days after coronary artery ligation. In a pathological setting, TNF-alpha inhibits the proliferative response of endothelial cells through inactivation of receptors for vascular endothelial growth factor (VEGF). Growth of HUVEC trarisfected with sTNFRI vector increased significantly compared to those transfected with control vector. The TNF-alpha-induced internucleosomic fragmentation was also significantly prevented in HUVEC transfected with sTNFRI vector compared to those trarisfected with control vector. In a rat model of hindlimb ischemia, VEGF increased but activation of KDR/flk-1 was suppressed possibly by TNF-alpha, which might impair angiogenesis. Suppression of TNF-alpha with sTNFR1 plasmid upregulated KDR/flk-1 and accelerated angiogenesis.

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] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction."FASEB Journal. 16. 1421-1422 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-α receptor I gene."Atherosclerosis. 162. 77-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."Journal of Cardiovascular Pharmacology. 40. 146-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular gene transfer of soluble TNF-alpha reeptor 1 activates vascular endothelial growth factor receptor (KDR/flk-1) and accelerates angiogenesis in a rat model of hindlimb ischemia."Circulation. 103. 797-802 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alfa receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Molecular Cellular Biochemistry. 258. 57-63 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction."FASEB Journal.. 16. 1421-1422 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-α receptor I gene."A therosclerosis.. 162. 77-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."Journal of Cardiovascular Pharmacology. 40. 146-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular gene transfer of soluble TNF-alpha receptor 1 activates vascular endotbelial growth factor receptor (KDR/flk-1) and accelerates angiogenesis in a rat model of hindlimb ischemia."Circulation.. 103. 797-802 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alpha receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Molecular Cellular Biochemistry. 258. 57-63 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction."FASEB Journal. 16. 1421-1422 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-α receptor I gene."Atherosclerosis. 162. 77-84 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."Journal of Cardiovascular Pharmacology. 40. 146-152 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular gene transfer of soluble TNF-alpha receptor 1 activates vascular endothelial growth factor receptor (KDR/flk-1) and accelerates angiogenesis in a rat model of hindlimb ischemia."Circulation. 103. 797-802 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alpha receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Molecular Cellular Biochemistry. 258. 57-63 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Hata T, Makino N.: "In vivo transfer of soluble TNF-alpha receptor 1 gene improves cardiac function and reduces infarct size after myocardial infarction in rats"FASEB Journal. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction"FASEB J. 16. 1421-1422 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor I gene"Atherosclerosis. 162. 77-84 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL"J Cardiovasc Pharmacol.. 40. 146-152 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh S., Ueda Y, Koyanagi, M, Kadokami T, Sugano M., Makino N.: "Chronic inhibition of Rho kinase blunts the process of left ventricular hypertrophy leading to cardiac contractile dysfunction in hypertension-induced heart failure"J Mol Cell Cardiol. 35. 59-70 (2003)

    • Related Report
      2002 Annual Research Report

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

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