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Exploring the new mechanisms of pulmonary hypertension with Liver RNA sequencing

Research Project

Project/Area Number 20K17137
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Asano Ryotaro  国立研究開発法人国立循環器病研究センター, 病院, 非常勤研究員 (60827004)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺高血圧症 / 網羅的遺伝子発現 / RNAシークエンス
Outline of Research at the Start

肺動脈性高血圧症(PAH)は原因不明に肺動脈リモデリングを生じ、右心不全から死に至る難病である。腸管から吸収された物質が肝臓に輸送されない門脈結紮モデルでは肺高血圧症病態が大幅に改善することから、PAH病態において腸-肝-肺連関が重要であると仮説を立てた。そこで肝障害モデル動物への肺高血圧負荷やPAH患者検体を通じて、PAHの新規病態形成機序を探索する。

Outline of Final Research Achievements

Pulmonary hypertension causes remodeling of the pulmonary arteries in association with a variety of background diseases, including genetics, collagen disease, congenital heart disease, and liver injury. The mechanism of pulmonary artery remodeling is still unknown, but it is likely that some common pathway of background disease is impaired to form the pulmonary hypertension pathology. The liver is the largest organ in the human body, that is closely linked to multiple organs, and it has been reported that it may also play an important role in pulmonary hypertension. In this study, through liver RNA sequencing analysis of animal models and comprehensive analysis of pulmonary hypertension patient samples, we found that the protective gene X in the liver plays an important role in pulmonary hypertension.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、肝臓は肺高血圧症の病態形成機構の中でも重要な役割を果たしていることが裏づけられた。特に遺伝子Xは、肝臓での代謝関連する、肺高血圧症の保護的遺伝子であることを見出した。これにより近年注目を集める門脈圧亢進に伴う肺高血圧症を中心として肺高血圧症全般の新たなバイオマーカーや治療法開発につながる可能性がある。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (2 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models2022

    • Author(s)
      Waddingham Mark T.、Tsuchimochi Hirotsugu、Sonobe Takashi、Asano Ryotaro、Jin Huiling、Ow Connie P. C.、Schwenke Daryl O.、Katare Rajesh、Aoyama Kohki、Umetani Keiji、Hoshino Masato、Uesugi Kentaro、Shirai Mikiyasu、Ogo Takeshi、Pearson James T.
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 1-15

    • DOI

      10.3389/fphys.2021.766818

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension2021

    • Author(s)
      Masaki T, Okazawa M, Asano R, Inagaki T, Ishibashi T, Yamagishi A, Umeki-Mizushima S, Nishimura M, Manabe Y, Ishibashi-Ueda H, Shirai M, Tsuchimochi H, Pearson JT, Kumanogoh A, Sakata Y, Ogo T, Kishimoto T, Nakaoka Y
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 118 Issue: 11

    • DOI

      10.1073/pnas.2023899118

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological and clinical effects of interleukin-6 on human myocarditis2021

    • Author(s)
      Amioka Naofumi、Nakamura Kazufumi、Kimura Tomonari、Ohta-Ogo Keiko、Tanaka Takehiro、Toji Tomohiro、Akagi Satoshi、Nakagawa Koji、Toh Norihisa、Yoshida Masashi、Miyoshi Toru、Nishii Nobuhiro、Watanabe Atsuyuki、Asano Ryotaro、Ogo Takeshi、Nakaoka Yoshikazu、Morita Hiroshi、Yanai Hiroyuki、Ito Hiroshi
    • Journal Title

      Journal of Cardiology

      Volume: 78 Issue: 2 Pages: 157-165

    • DOI

      10.1016/j.jjcc.2021.03.003

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic value of right ventricular native T1 mapping in pulmonary arterial hypertension2021

    • Author(s)
      Asano Ryotaro、Ogo Takeshi、Morita Yoshiaki、Kotoku Akiyuki、Aoki Tatsuo、Hirakawa Kyoko、Nakayama Sayuri、Ueda Jin、Tsuji Akihiro、Waddingham Mark T.、Ohta Yasutoshi、Fukuda Tetsuya、Ohta-Ogo Keiko、Ishibashi-Ueda Hatsue、Noguchi Teruo、Yasuda Satoshi
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 11 Pages: e0260456-e0260456

    • DOI

      10.1371/journal.pone.0260456

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pristane/Hypoxia (PriHx) Mouse as a Novel Model of Pulmonary Hypertension Reflecting Inflammation and Fibrosis2020

    • Author(s)
      Mori Hiroyoshi、Ishibashi Tomohiko、Inagaki Tadakatsu、Okazawa Makoto、Masaki Takeshi、Asano Ryotaro、Manabe Yusuke、Ohta-Ogo Keiko、Narazaki Masashi、Ishibashi-Ueda Hatsue、Kumanogoh Atsushi、Nakaoka Yoshikazu
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 7 Pages: 1163-1172

    • DOI

      10.1253/circj.CJ-19-1102

    • NAID

      130007864283

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-06-25
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸内細菌叢変容は肺高血圧症病態の重要な予後関連因子である2021

    • Author(s)
      浅野遼太郎
    • Organizer
      第6回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Aryl hydrocarbon receptor and gut microbiome in the pathogenesis of pulmonary arterial hypertension2021

    • Author(s)
      Yoashikazu Nakaoka
    • Organizer
      Basic CardioVascular Research 2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 肺高血圧症改善用組成物、肺高血圧症の予後予測方法、肺 高血圧症の重症度判定補助方 法および肺高血圧症の診断 補助方法2021

    • Inventor(s)
      中岡良和、浅野遼太郎、大郷剛
    • Industrial Property Rights Holder
      中岡良和、浅野遼太郎、大郷剛
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 肺高血圧症改善用組成物、肺高血圧症の予後予測方法、肺 高血圧症の重症度判定補助方法および肺高血圧症の診断 補助方法2021

    • Inventor(s)
      中岡 良和,浅野 遼太郎,大郷 剛
    • Industrial Property Rights Holder
      中岡 良和,浅野 遼太郎,大郷 剛
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report
    • Overseas

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Published: 2020-04-28   Modified: 2023-01-30  

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