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Molecular mechanisms involved in the pathogenesis of occlusive pulmonary vasculopathy

Research Project

Project/Area Number 24591574
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionMie University

Principal Investigator

MITANI Yoshihide  三重大学, 医学部附属病院, 准教授 (60273380)

Co-Investigator(Kenkyū-buntansha) SAWADA Hirofumi  三重大学, 医学(系)研究科(研究院), 講師 (30362354)
MARUYAMA Kazuo  三重大学, 医学(系)研究科(研究院), 教授 (20181828)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords小児科学 / 小児循環器学 / 肺高血圧 / 動物モデル / ラットモデル / 増悪 / 退縮 / 細胞死
Outline of Final Research Achievements

Project 1-Phenotypically Modulated Smooth Muscle Cells and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy in Rats -: We tested the hypothesis that phenotypically modulated smooth muscle cells (SMCs) and related inflammation are associated with the progression of experimental occlusive pulmonary vascular disease (PVD). We concluded that phenotypically modulated SMCs and related inflammation are associated with the progression of experimental obstructive PVD.
Project 2-Macitentan reverses early obstructive pulmonary vasculopathy in rats-
We test the hypothesis that a novel endothelin receptor antagonist macitentan reverses the early and/or late stages of occlusive pulmonary vascular disease (PVD) in rats. In conclusion, macitentan reversed early but not late obstructive PVD in rats. This reversal was associated with the suppression of survivin-related resistance to apoptosis and proliferation of cells in PVD.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (21 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 7 results)

  • [Journal Article] Potential Contribution of Phenotypically Modulated Smooth Muscle Cells and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy in Rats.2015

    • Author(s)
      Otsuki S, Sawada H, Yodoya N, Shinohara T, Kato T, Ohashi H, Zhang E, Imanaka-Yoshida K, Shimpo H, Maruyama K, Komada Y, Mitani Y.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 2 Pages: 0118655-0118655

    • DOI

      10.1371/journal.pone.0118655

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macitentan reverses early obstructive pulmonary vasculopathy in rats: early intervention in overcoming the survivin-mediated resistance to apoptosis.2015

    • Author(s)
      Shinohara T, Sawada H, Otsuki S, Yodoya N, Kato T, Ohashi H, Zhang E, Saitoh S, Shimpo H, Maruyama K, Komada Y, Mitani Y.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 308(6) Issue: 6 Pages: L523-L538

    • DOI

      10.1152/ajplung.00129.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effect of thrombomodulin on the development of monocrotaline-induced pulmonary hypertension.2014

    • Author(s)
      Yamada Y, Maruyama J, Zhang E, Maruyama K. et al
    • Journal Title

      J Anesth

      Volume: 28(1) Issue: 1 Pages: 26-33

    • DOI

      10.1007/s00540-013-1663-z

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Circumstances and Outcomes of Out-Of-Hospital Cardiac Arrest in Elementary and Middle School Students in the Era of Public-Access Defibrillation: Implications for Emergency Preparedness in Schools2014

    • Author(s)
      Mitani Y, Ohta K, Ichida F, Nii M, Arakaki Y, Ushinohama H, Takahashi T, Ohashi H, Yodoya N, Fujii E, Ishikura K, Tateno S, Sato S, Suzuki T, Higaki T, Iwamoto M, Yoshinaga M, Nagashima M, Sumitomo N
    • Journal Title

      Circulation J

      Volume: 78(3) Pages: 701-707

    • NAID

      130003391007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension.2014

    • Author(s)
      Sawada H, Saito T, Nickel NP, Alastalo TP, Glotzbach JP, Chan R, Haghighat L, Fuchs G, Januszyk M, Cao A, Lai YJ, Perez Vde J, Kim YM, Wang L, Chen PI, Spiekerkoetter E, Mitani Y, Gurtner GC, Sarnow P, Rabinovitch M.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 211 Issue: 2 Pages: 263-280

    • DOI

      10.1084/jem.20111741

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Public access defibrillation improved the outcome after out-of-hospital cardiac arrest in school-age children: a nationwide, population-based, Utstein registry study in Japan2013

    • Author(s)
      Mitani Y, Ohta K, Yodoya N, Otsuki S, Ohashi H, Sawada H, Nagashima M, Sumitomo N, Komada Y.
    • Journal Title

      Europace

      Volume: 15 Issue: 9 Pages: 1259-66

    • DOI

      10.1093/europace/eut053

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 小児期肺高血圧と先天性心疾患に伴う肺血管病変:An update2013

    • Author(s)
      三谷義英
    • Journal Title

      日本小児循環器学会雑誌

      Volume: 29(1) Pages: 17-26

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 長期経過した川崎病既往児に対する対応2012

    • Author(s)
      三谷義英
    • Journal Title

      小児科臨床

      Volume: 65 Pages: 1611-1619

    • Related Report
      2012 Research-status Report
  • [Journal Article] 肺動脈性高血圧の最近の知見:血管医学の新しい研究領域2012

    • Author(s)
      三谷義英
    • Journal Title

      血管

      Volume: 35 Pages: 105-114

    • NAID

      10031128076

    • Related Report
      2012 Research-status Report
  • [Journal Article] 学校心停止とAED2012

    • Author(s)
      三谷義英
    • Journal Title

      救急医学

      Volume: 36 Pages: 1668-1671

    • Related Report
      2012 Research-status Report
  • [Presentation] Ask the Experts: What is the Cellular Target in Occlusive Pulmonary Vasculopathy ?: New Insights Immature Smooth Muscle Cells2015

    • Author(s)
      Mitani Y
    • Organizer
      American Heart Association
    • Place of Presentation
      Orland, US
    • Year and Date
      2015-11-08 – 2015-11-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Macitentan Reverses Early Obstructive Pulmonary Vasculopathy in Rats: Early Intervention in Overcoming the Survivin-mediated Resistance to Apoptosis2015

    • Author(s)
      Shinohara T., Sawada H., Otsuki S., Yodoya N., Kato T., Ohashi H., Zhang E., Saitoh S., Shimpo H., Maruyama K., Komada Y., Mitani Y.
    • Organizer
      Association for European Pediatric and Congenital Cardiology
    • Place of Presentation
      Peague, Czech Republic
    • Year and Date
      2015-05-20 – 2015-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Phenotypic Modulation of Smooth Muscle Cells and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy in Rats.2013

    • Author(s)
      Otsuki S, Sawada H, Yodoya N, Shinohara T, Kato T, Ohashi H, Zhang E, Yoshida-Imanaka K, Shimpo H, Maruyama K, Komada Y, Mitani Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      米国
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Early detection of pediatric idiopathic pulmonary arterial hypertension by school electrocardiography screening: a nationwide survey in Japan.2013

    • Author(s)
      Sawada H, Mitani Y, Nakayama T, Fukushima H, Kogaki S, Igarashi T, Ichida F, Ono Y, Nakanishi T, Doi S, Ishikawa S, Matsushima M, Yamada O, Saji T.
    • Organizer
      American Heart Association
    • Place of Presentation
      米国
    • Related Report
      2013 Research-status Report
  • [Presentation] Medical treatment of pulmonary arterial hypertension and pulmonary vascular disease associated with congenital heart disease2013

    • Author(s)
      Mitani Y
    • Organizer
      The 21th meeting of the Asian Society for Cardiovascular and Thoracic Surgery
    • Place of Presentation
      Kobe
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Reduced BMPR-II Induces GM-CSF Translation and Macrophage Recruitement in Human and Mice, Exacerbating Pulmonary Hypertension.2013

    • Author(s)
      Hirofumi Sawada, Yoshihide Mitani, Noriko Yodoya, Shoichiro Otsuki1, Hiroyuki Ohashi, Kazuo Maruyama, Yoshihiro Komada, Marlene Rabinovitch.
    • Organizer
      第2回日本肺循環学会
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Bosentan ameliorates pulmonary hypertension in mice by modulating stem cell kinetics and related gene expression: a new therapeutic target.2013

    • Author(s)
      Kato T, Mitani Y
    • Organizer
      The 77th Scientific meetig of the Japanese Circulation Society
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Invited
  • [Presentation] Medical treatment of pulmonary arterial hypertension and pulmonary vascular disease associated with congenital heart disease.2013

    • Author(s)
      Mitani Y
    • Organizer
      The 21th meeting of the Asian Society for Cardiovascular and Thoracic Surgery
    • Place of Presentation
      Kobe
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Pre-event Course of Culprit Lesions in Acute Coronary Syndrome in Adults with a History of Kawasaki Disease: A Nationwide Survey2013

    • Author(s)
      Yoshihide Mitani, Etsuko Tsuda, Mamoru Ayusawa, Touru Kobayashi, Fukiko Ichida, Masaki Matsushima, Takashi Higaki, Kenji Suda, Hiroyoshi Yokoi, Kenji Hamaoka
    • Organizer
      The 77th Scientific meetig of the Japanese Circulation Society
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of endogenous bone marrow-derived stem cells and its pharmacological modulation in pulmonary arterial hypertension in mice: a new mechanism of action in bosentan therapy.2012

    • Author(s)
      Taichi Kato, Hirofumi Sawada, Hiroyuki Ohashi, Shoichiro Otsuki, Noriko Yodoya, Hideto Shimpo, Yoshihiro Komada, Yoshihide Mitani.
    • Organizer
      American Heart Association
    • Place of Presentation
      LA
    • Related Report
      2012 Research-status Report
  • [Presentation] Public access defibrillation improved the outcome after out-of-hospital cardiac arrests in school-age children: a nationwide, population-based, Utstein registry study in Japan2012

    • Author(s)
      Yoshihide Mitani, Kunio Ohta, Noriko Yodoya, Shoichiro Otsuki, Hiroyuki Ohashi, Hirofumi Sawada, Masami Nagashima, Naokata Sumitomo, Yoshihiro Komada,
    • Organizer
      American Heart Association
    • Place of Presentation
      LA
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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