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Angiopoietin-1 gene therapy for acute myocardial infarction

Research Project

Project/Area Number 15590761
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ITO Yoshinori  Sapporo Medical University, Medicine, Instructor, 医学部, 助手 (80332914)

Co-Investigator(Kenkyū-buntansha) MORIKAWA Masayuki  SAPPORO MEDICAL UNIVERSITY, Medicine, Assistant Prof., 医学部, 助教授 (60264537)
HAMADA Hirofumi  SAPPORO MEDICAL UNIVERSITY, Medicine, Professor, 医学部, 教授 (00189614)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsGene Therapy / Myocardial Infarction / Ischemic Heart Disease / Viral Vector / Angiopoietin-1 / VEGF / 間葉系幹細胞
Research Abstract

In acute myocardial infarction (AMI), prognosis and the mortality rate are closely related to the infarct size, and the progression of post-infarction cardiac failure. Angiogenic gene-therapy has presented a new approach for the treatment of AMI. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that gene-therapy of Angl for AMI might promote angiogenesis cooperatively with intrinsic VEGF.
To evaluate the therapeutic effects of Angi in AMI, we employed a rat AMI model, and adenoviral Angi gene transfer to the heart. A significant increase in capillary density, and reduction in infarct size were noted in the infarct hearts with adenoviral Angi gene treatment. Furthermore, Angl group showed significantly higher cardiac performance. The adenoviral delivery Angi during the acute phase of myocardial infarction would be feasible to attenuate the pr … More ogression of cardiac dysfunction in the rat model without unfavorable effects. However, adverse effects of adenoviral vector might be concern for clinical use of Angl gene therapy for AIVII. For this purpose, we evaluated naked plasmid injection and Sendai virus vector (SeVV) as an alternative gene delivery method of adenoviral vector. In our results, transgene expression mediated by naked CA promoter-based plasmid injection and SeVV were shown to be quite efficient in the heart. Similarly with adenoviral Angl gene therapy, Angi gene delivery for infarct heart utilizing SeVV or naked plasmid injection clearly promoted myocardial angiogenesis and reduced the infarct size resulting in the prevention of remodeling. Especially, SeVV'mediated Angi gene therapy demonstrated early recovery (within 3 days) of ischemic event. Furthermore transplantation of bone marrow mesenchymal stem cells (MSC) modified with Angl gene was more efficient for the recovery of ischemia in comparison with gene therapy or MSCs transplantation alone.
Naked plasmid or Sendai virus vector encoding angiopoietin-1 gene would be safe and useful therapeutic option for acute myocardial infarction. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (28 results)

All 2005 2004 2003 Other

All Journal Article (22 results) Publications (6 results)

  • [Journal Article] Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.2005

    • Author(s)
      Kurozumi K, Ito Y, et al.
    • Journal Title

      Mol Ther. 11・1

      Pages: 96-104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model2005

    • Author(s)
      Kurozumi K, Ito Y, et al.
    • Journal Title

      Mol Ther. 11(1)

      Pages: 96-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.2004

    • Author(s)
      Kurozumi K, Ito Y, et al.
    • Journal Title

      Mol Ther 9(2)

      Pages: 189-197

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-beta2m-/- repopulating cells.2004

    • Author(s)
      Kobune M, Ito Y, et al.
    • Journal Title

      Blood 104・4

      Pages: 1002-1009

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model.2004

    • Author(s)
      Nakamura K, Ito Y, et al.
    • Journal Title

      Gene Ther. 11・14

      Pages: 1155-1164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells.2004

    • Author(s)
      Chiba H, Ito Y, et al.
    • Journal Title

      Exp Hematol. 32・12

      Pages: 1194-1203

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model2004

    • Author(s)
      Kurozurru K, Ito Y, et al.
    • Journal Title

      Mol Ther. 9(2)

      Pages: 189-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-beta2m-/-repopulating cells2004

    • Author(s)
      Kobune M, Ito Y, et al.
    • Journal Title

      Blood. 104(4)

      Pages: 1002-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model2004

    • Author(s)
      Nakamura K, Ito Y, et al.
    • Journal Title

      Gene Ther. 11(14)

      Pages: 1155-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells2004

    • Author(s)
      Chiba H, Ito Y, et al.
    • Journal Title

      Exp Hematol. 32(12)

      Pages: 1194-203

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Combined administration of basic fibroblast growth factor protein and the hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.2004

    • Author(s)
      Ono I, Ito Y, et al.
    • Journal Title

      Wound Repair Regen 12・1

      Pages: 67-79

    • NAID

      10016984516

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy2004

    • Author(s)
      Ono I, Ito Y, et al.
    • Journal Title

      Biomaterials 25・19

      Pages: 4709-4718

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells.2003

    • Author(s)
      Kobune M, Ito Y, et al.
    • Journal Title

      Exp Hematol 31(8)

      Pages: 715-722

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenoviral delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction.2003

    • Author(s)
      Takahashi K, Ito Y, et al.
    • Journal Title

      Mol Ther 8(4)

      Pages: 584-592

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Myocardial injection of CA promoter-based plasmid mediates efficient transgene expression in rat heart.2003

    • Author(s)
      Huang JH, Ito Y, et al.
    • Journal Title

      J Gene Med 5(10)

      Pages: 900-908

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bcl-xL Gene Transfer Protects the heart against Ischemia / Reperfusion Injury.2003

    • Author(s)
      Huang J, Ito Y, et al.
    • Journal Title

      Biochemi Biophys Res Commun 311

      Pages: 64-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model.2003

    • Author(s)
      Yamauchi A, Ito Y, et al.
    • Journal Title

      J Gene Med 5(11)

      Pages: 994-1004

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-upporting cells2003

    • Author(s)
      Kobune M, Ito Y, et al.
    • Journal Title

      Exp Hematol. 31(8)

      Pages: 715-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenoviral-delivered angiopoietin-I reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction2003

    • Author(s)
      Takahashi K, Ito Y, et al.
    • Journal Title

      Mol Ther. 8(4)

      Pages: 584-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Myocardial injection of CA promoter-based plasmid mediates efficient transgene expression in rat heart2003

    • Author(s)
      Huang J, Ito Y, et al.
    • Journal Title

      J Gene Med. 5(10)

      Pages: 900-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bc-xL gene transfer protects the heart against ischemia/reperfusion injury2003

    • Author(s)
      Huang J, Ito Y, et al.
    • Journal Title

      Biochem Biophys Res Common. 311(1)

      Pages: 64-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pre-adrninistration of angiopoietiir1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model2003

    • Author(s)
      Yamauchi A, Ito Y, et al.
    • Journal Title

      J Gene Med. 5(11)

      Pages: 994-1004

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kobune M, Ito Y, et al.: "Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells."Exp Hematol. 31(8). 715-722 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi K, Ito Y, et al.: "Adenoviral delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction."Mol Ther. 8(4). 584-592 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Huang JH, Ito Y, et al.: "Myocardial injection of CA promoter-based plasmid mediates efficient transgene expression in rat heart."J Gene Med. 5(10). 900-908 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Huang J, Ito Y, et al.: "Bcl-xL Gene Transfer Protects the heart against Ischemia / Reperfusion Injury."Biochemi Biophys Res Commun. 311. 64-70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamauchi A, Ito Y, et al.: "Pre-administration of angiopoietin-1 followed by VEGE induces functional and mature vascular formation in a rabbit ischemic model."J Gene Med. 5(11). 994-1004 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurozumi K, Ito Y, et al.: "BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model."Mol Ther. 9(2). 189-197 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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