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Development of novel therapeutic target in chronic thromboembolic pulmonary hypertension

Research Project

Project/Area Number 15K19360
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionTohoku University

Principal Investigator

Yaoita Nobuhiro  東北大学, 東北メディカル・メガバンク機構, 助教 (00735368)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords循環器・高血圧 / 肺高血圧症 / 血栓 / 線溶系
Outline of Final Research Achievements

The clot of chronic thromboembolic pulmonary hypertension (CTEPH) patients was more resistant to fibrinolysis than that of non-PH patients or pulmonary arterial hypertension (PAH)patients. The plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) and the activation of TAFI were increased in CTEPH patients. Moreover, SNPs of cpb2, which induced the plasma levels of TAFI, was found in CTEPH patients. The impairment of fibrinolysis in CTEPH patients was inmproved with the inhibitor of avtivated TAFI.
In the TAFI overexpression mice, pulmonary hypertension was worse than wild type mice with hypoxic exposure and organaized thrombi ws found in pulmonary artery. Moreoover, TAFI increased the proliferation of smooth muscle cells of human.
These data suggest that TAFI could be a novel biomarker and realistic therapeutic target of CTEPH.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Activated TAFI promotes the development of chronic thromboembolic pulmonary hypertension - A possible novel therapeutic target -2017

    • Author(s)
      Satoh T, Satoh K, Yaoita N, Kikuchi N, Omura J, Kurosawa R, Numano K, Elias-Al-Mamun M, AbdulHai Siddique MAH, Sunamura S, Nogi M, Suzuki K, Miyata S, John Morser J, Shimokawa H.
    • Journal Title

      Circ Res.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Thrombin-activatable fibrinolysis inhibitor in chronic thromboembolic pulmonary hypertension.2016

    • Author(s)
      Yaoita N, Satoh K, Satoh T, Sugimura K, Tatebe S, Yamamoto S, Aoki T, Miura M, Kawamura T, Horiuchi H, Fukumoto Y, Shimokawa H.
    • Journal Title

      Arterioscler Throm Vasc Biol.

      Volume: 36 Pages: 1293-1301

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel Therapeutic Targets of Pulmonary Hypertension.2016

    • Author(s)
      Yaoita N, Satoh K, Shimokawa H.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 36

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Multiple Beneficial Effects of Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension2016

    • Author(s)
      Tatebe S, Sugimura K, Aoki T, Miura M, Nochioka K, Miyamichi-Yamamoto S, Yaoita N, Suzuki H, Sato H, Satoh K, Fukumoto Y, Shimokawa H.
    • Journal Title

      Circulation Journal

      Volume: 80 Issue: 4 Pages: 980-988

    • DOI

      10.1253/circj.CJ-15-1212

    • NAID

      130005139581

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Thrombin Activatable Fibrinolysis Inhibitor Promotes Development of Chronic Thromboembolic Pulmonary Hypertension-A Possible Novel Therapeutic Target.2016

    • Author(s)
      T Satoh, K Satoh, N Yaoita, N Kikuchi, J Omura, R Kurosawa, S Sunamura, M Nogi, T Otsuki, K Numano, Elias Al-Mamun, Mohammad Abdul Hai Siddique, S Tatebe, T Aoki, K Sugimura, J Morser, H Shimokawa
    • Organizer
      アメリカ心臓病学会
    • Place of Presentation
      ニューオーリンズ(アメリカ)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crucial Role of Thrombin-Activated Fibrinolysis Inhibitor in the Pathogenesis of Chronic Thromboembolic Pulmonary Hypertension2016

    • Author(s)
      Nobuhiro Yaoita, Kimio Satoh, Taijyu Satoh, Nobuhiro Kikuchi, Junichi Omura, Ryo Kurosawa, Masamichi Nogi, Tomohiro Otsuki, Katsuya Kozu, Kazuhiko Numano, Kota Suzuki, Shinichiro Sunamura, Shunsuke Tatebe, Tatsuo Aoki, Koichiro Sugimura, Hisanori Horiuchi, Hiroaki Shimokawa
    • Organizer
      日本循環器学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Influence of Discontinuation of Medications after Successful Percutaneous Transluminal Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension2016

    • Author(s)
      Nobuhiro Yaoita, Koichiro Sugimura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Masanobu Miura, Kimio Satoh, Hiroaki Shimokawa
    • Organizer
      日本循環器学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Thrombin-activated Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension2015

    • Author(s)
      Nobuhiro Yaoita, Kimio Satoh, Taijyu Satoh, Koichiro Sugimura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Masanobu Miura, Takeshi Kawamura, Hisanori Horiuchi, Yoshihiro Fukumoto, Hiroaki Shimokawa
    • Organizer
      American Heart Association
    • Place of Presentation
      アメリカ(オーランド)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Crucial Role of Thrombin-activated Fibrinolysis Inhibitor in the Pathogenesis of Chronic Thromboembolic Pulmonary Hypertension2015

    • Author(s)
      Nobuhiro Yaoita, Taijyu Satoh, Kimio Satoh, Koichiro Sugimura,Shunsuke Tatebe,Saori Yamamoto,Tatsuo Aoki, Masanobu Miura, Yoshihiro Fukumoto, Hisanori Horiuchi, Hiroaki Shimokawa
    • Organizer
      European Respiratory Society
    • Place of Presentation
      オランダ(アムステルダム)
    • Year and Date
      2015-09-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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