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Gene therapy to prevent vascular remodeling-vascular smooth muscle cell as a target cell

Research Project

Project/Area Number 14570663
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TANIGUCHI Takahiro  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Assistant Professor, 医学部附属病院, 講師 (20263379)

Co-Investigator(Kenkyū-buntansha) KAWASHIMA Seinosuke  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10177678)
ISHIKAWA Yuichi  Kobe University Graduate School of Medicine, Division of Health Sciences, Professor, 医学部, 教授 (90159707)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordssmooth muscle cell / differentiation / restenosis / gene therapy / vascular remodeling / stent / 血管形成術後再狭窄 / ヒストン脱アセチル化酵素阻害剤 / p21蛋白
Research Abstract

Vascular smooth muscle cell (VSMC) migration, proliferation, and matrix synthesis within the intima of vessels play an important role in post-angioplasty restenosis. Coronary artery restenosis remains a major unresolved limitation for interventional cardiology. It results from arterial injury incurred during coronary vascularization and is caused in large part bu neointimal hyperplasia, especially within stents. To develop a new therapeutic strategy, we performed following studies. Akt (PKB) is a serine-threonine protein kinase that is activated by various extracellular stimuli through the phosphatidylinositol 3-kinase (P1 3-kinase) pathway. Akt plays an important role in apoptosis, cell proliferation, glucose metabolism and angiogenesis. VSMCs have three isoforms of myosine heavy chains : SM 1,SM 2 and SM emb. After angioplasty, VSMCs change their phenotype from differentiated phenotype (SM 1 and SM 2) to dedifferentiated one (SM emb). Akt regulates these VSMC phenotypic changes. Aden … More oviral transduction of constitutive-active Akt 1 (Adeno-myrAkt) increased expression of SM 1 and SM2. Conversely, dominant-negative Akt 1 increased SMemb expression. Next, we try to transfect target gene to VSMCs in vivo. Metallic stents coated with a polyurethane emulsion containing plasmid DNA were implanted in rabbit femoral arteries to evaluate transgene delivery and expression in the vessel wall. The expression of the plasmid-encoded marker genes, β-galactosidase, luciferase and green fluorescence protein (GEP), were evaluated at 7 days after implantation. The extent of transgene expression was dependent upon the quantity of DNA loaded onto the stent, no signal was detected in vessel segments that received bare metallic stents or polymer-coated stents lacking plasmid DNA. Finally, co-localization studies identified transgene expression in both vascular smooth muscle cells and macrophages. These data demonstrate the utility of coated stents for the local, dose-dependent delivety of genes to multiple cell types in the vessel wall. Less

Report

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

Research Products

(21 results)

All Other

All Publications (21 results)

  • [Publications] Kawashima S: "HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats"Stroke. 34. 157-163 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sata M: "Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway"Arterioscler Thromb Vasc Biol. 22・8. 1305-1309 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaishi H: "High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells"Biochemi Biophys Rese Comm. 305. 122-128 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Domoto K: "Chylomicron remnants induce monocyte chemoattractant protein-1 expression via p38 MAPK activation in vascular smooth muscle cells"Atherosclerosis. 171. 193-200 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 川嶋成乃亮: "脈管疾患の病態における内皮型NO合成酵素の作用の多様性"脈管学. 42. 291-296 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 高橋 明広: "β-VLDL"高脂血症ナビゲーター. 110-111 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 高橋 明広: "動脈硬化"循環器疾患最新の治療. 433-438 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sata M: "Mouse genetic evidence that tranilast reduces smooth Muscle cell hyperplasia via a p21(WAFI)-dependent pathway"Arterioscler Thromb Vasc Biol. 22(8). 1305-1309 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawashima S: "HMG-CoA reductase inhibitor has protective effects Against stroke events in stoke-prone spontaneously hypertensive rats"Stroke. 34(1). 157-163 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaishi H: "High glucose accelerates MCP-1 production via p38 MAPK In vascular endothelial cells"Biochem Biophys Res Commun. 23:305(1). 122-128 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Domoto K: "Chylomicron remnants induce monocyte protein-1 Expression via p38 MAPK activation in vascular smooth muscle cells"Atherosclerosis. 171. 193-200 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi A: "Transgene delivery of plasmid DNA to smooth muscle Cells and macrophages from a biostable polymercoated stant"Gene Ther. 10(17). 1471-1478 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawashima S: "Dysfunction of endothelial nitric oxide synthase and Atherosclerosis"Arterioscler Thromb Vasc Biol.. 24. 1-8 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi A: "β-VLDL"Navigator for hyperlipidemia. 110-111 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi A: "New therapy for cardiovascular disease"Atherosclerosis. 433-438 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sata M: "Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via p21(waf-1)-dependent pathway"Arterioscler Thromb Vascc Biol. 22. 1305-1309 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takaishi H: "High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells"Biochemi Biophys Resse Comm. 305. 122-128 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 高橋 明広: "β-VLDL"高脂血症ナビゲーター. 110-111 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 高橋 明広: "動脈硬化"循環器疾患最新の治療. 2004-2005. 433-438 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawashima S: "HMG-CoA reductase inhibitor has protective effects against stroke events In stroke-prone spontaneously hypertensive rats"Stroke. 34. 157-163 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 川嶋成乃亮: "脈管疾患の病態における内皮型NO合成酵素の作用の多様性"脈管学. 42. 291-296 (2002)

    • Related Report
      2003 Annual Research Report

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Published: 2002-03-31   Modified: 2016-04-21  

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