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Development of novel treatment method forcardiovascular disorders with phenotype regulation of vascular cells using micro RNAs

Research Project

Project/Area Number 22390265
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKyoto University

Principal Investigator

MINAKATA Kenji  京都大学, 大学院・医学研究科, 講師 (60539675)

Co-Investigator(Kenkyū-buntansha) IKEDA Tadashi  京都大学, 大学院・医学研究科, 准教授 (40281092)
MARUI Akira  京都大学, 大学院・医学研究科, 准教授 (60402856)
TABATA Yasuhiko  京都大学, 再生医科学研究所, 教授 (50211371)
YAMAHARA Kenichi  国立循環器病研究センター, 再生医療部, 室長 (50450888)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsミクロRNA / 血管平滑筋 / 内膜肥厚 / miRNA / 虚血性心疾患 / 冠動脈バイパス術 / エレクトロポレーション / 血管リモデリング / レンチウイルス
Research Abstract

Intimal hyperplasia is the major cause of veingraft disease. Proliferation and migration of smooth muscle cells (SMCs) into the intima are key mechanism in this process. Recent studies have revealed that microRNA-145(miR-145) is a specific mediator in the regulation on phenotype of SMCs, proliferative or differentiative. We aimed to investigate the impact of miR-145 on intimal hyperplasia with rabbit vein graft disease model using electroporation-mediated gene transfer. We harvested right jugular vein of male Japanese white rabbit and injured the endothelium by balloon catheter. Vein graft was transduced with miR-145 encoding plasmidsby electroporator and interposed at ipsilateral carotid artery. Fourweeks after surgery, we explanted the venous graft and performed histological studies (hematoxylin and eosin staining, and elastica van Gieson staining for elastic fiber). Intimal thickness and intima/media area ratio were evaluated. Furthermore, immunohistochemistry for mature smooth muscle marker myosin heavy chain smooth muscle-1 and -2 (SM-1 and SM-2) and proliferation marker Ki-67 were performed to study the degree of differentiation and proliferation of SMCs.MiR-145 transduction significantly reduced neointimal thickness and intima/media area ratio compared to the grafts without gene transfer. Immunohistochemistry revealed that miR-145 transduced grafts contained more SM-2 positive mature SMCs and less Ki-67 positive proliferating cells. Considering these results, we conclude that electroporation-mediated non-virus transfer of miR-145 into the vein bypass graft potently regulates SMC phenotype and would be promising to prevent intimal hyperplasia in vein graft disease.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (20 results)

All 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (8 results) Remarks (2 results)

  • [Journal Article] Ventricular Approach for Functional Mitral Regurgitation in Cardiomyopathy2013

    • Author(s)
      Kenji Minakata.
    • Journal Title

      World Journal of Cardiovascular Surgery

      Volume: 3 Pages: 8-14

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Benefits of off-pump coronary artery bypass grafting in high-risk patients2012

    • Author(s)
      Marui A et al.
    • Journal Title

      Circulation

      Volume: 126

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of off-pump coronary artery bypass grafting compared with percutaneous coronary intervention: a propensity score analysis2012

    • Author(s)
      Marui A et al
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 41(1) Pages: 94-101

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gelatin nanospheres incorporating siRNA for controlled intracellular release2012

    • Author(s)
      Ishikawa H、Nakamura Y、Jo J、Tabata Y
    • Journal Title

      Biomaterials

      Volume: 33(35) Pages: 9097-9104

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of frequency of postoperative stroke in off-pump coronary artery bypass grafting versus on-pump coronary artery bypass grafting versus percutaneous coronary intervention.2012

    • Author(s)
      Marui A et al.
    • Journal Title

      Am J Cardiol

      Volume: 110 Issue: 12 Pages: 1773-1778

    • DOI

      10.1016/j.amjcard.2012.08.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of off-pump coronary artery bypass grafting compared with percutaneous coronary intervention: a propensity score analysis.2012

    • Author(s)
      Marui A et al.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 41 Pages: 94-101

    • DOI

      10.1016/j.ejcts.2011.04.004

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of microRNA-145 in human embryonic stem cell differentiation into vascular cells2011

    • Author(s)
      Yamaguchi S、Yamahara K et al、
    • Journal Title

      Atherosclerosis

      Volume: 219(2) Pages: 468-74

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] of microRNA-145 in human embryonic stem cell differentiation into vascu2011

    • Author(s)
      Shintaro Y, Yamahara K, et al
    • Journal Title

      Atherosclerosis

      Volume: 219 Pages: 468-474

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管平滑筋分化とマイクロRNA2011

    • Author(s)
      山原研一, ほか
    • Journal Title

      血管医学

      Volume: 12巻3号 Pages: 33-37

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Carvedilol may alleviate late cardiac remodeling following surgical ventricular restoration2010

    • Author(s)
      Yoshikawa E、Marui A、Tsukashita M、Nisina T、Wang J、Muranaka H、Ikeda T、Komeda M
    • Journal Title

      European Journal of Cardiothoracic Surgery

      Volume: 37(2) Pages: 362-367

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] 、microRNA-145 Prevents Intimal Hyperplasia in Rabbit Vein Graft Disease Model by Regulation of Smooth Muscle Cell Phenotype2013

    • Author(s)
      Ohnaka M、Marui A、Yamahara K、Minakata K、Yamazaki K、Kumagai M、Masumoto H、IkedaT、Sakata R、Poster1
    • Organizer
      The 21st Annual Meeting Of The Asian Society For Cardiovascular And Thoracic Surgery (ASCVTS2013)
    • Place of Presentation
      Kobe、Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] MicroRNA-145 prevents intimal hyperplasia in Rabbit vein graft disease model by regulation of smooth muscle cell phenotype2013

    • Author(s)
      大仲玄明
    • Organizer
      Annual Meeting Of The Asian Society For Cardiovascular And Thoracic Surgery (ASCVTS2013)
    • Place of Presentation
      Kobe,Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of MicroRNA - 145 to prevent vein graft disease in rabbit by regulation of smooth muscle cell phenotype2012

    • Author(s)
      Ohnaka M、Marui A、Yamahara K、 Ikeda Tet al
    • Organizer
      American Heart Association 、 Scientific Sessions 2012 (AHA 84th)
    • Place of Presentation
      Los Angeles、USA、
    • Related Report
      2012 Final Research Report
  • [Presentation] Impact of MicroRNA-145 to prevent vein graft disease in Rabbit by regulation of smooth muscle cell phenotype2012

    • Author(s)
      大仲玄明
    • Organizer
      American Heart Association,Scientific Sessions 2012 (AHA 84th)
    • Place of Presentation
      Los Angeles, USA.
    • Related Report
      2012 Annual Research Report
  • [Presentation] The role of microRNA-145 in the differentiation of human embryonic stem cells into smooth muscle cells2011

    • Author(s)
      K.Yamahara, et al
    • Organizer
      欧州心臓病学会2011
    • Place of Presentation
      仏・パリ
    • Year and Date
      2011-08-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトES細胞由来血管構成細胞におけるmicroRNA 145の役割2011

    • Author(s)
      山原研一, ほか
    • Organizer
      第11回日本抗加齢医学会総会
    • Place of Presentation
      京都市(国立京都国際会館)
    • Year and Date
      2011-05-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of Microrna-145 in human embryonic stem cell differentiation into smooth muscle cells2010

    • Author(s)
      K Yamahara, et al
    • Organizer
      米国心臓病学会2010
    • Place of Presentation
      米国・シカゴ
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒトES細胞由来血管平滑筋細胞の分化誘導におけるmiR-145の役割2010

    • Author(s)
      山原研一, ほか
    • Organizer
      第33回日本高血圧学会総会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Year and Date
      2010-10-15
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.kyoto-cvs.jp/study/03/

    • Related Report
      2012 Final Research Report
  • [Remarks] 京都大学 心臓血管外科

    • URL

      http://www.kyoto-cvs.jp/

    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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