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Role of long noncoding RNA in the pulmonary artery hypertension

Research Project

Project/Area Number 21K08033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNagasaki University

Principal Investigator

MAEMURA Koji  長崎大学, 医歯薬学総合研究科(医学系), 教授 (90282649)

Co-Investigator(Kenkyū-buntansha) 池田 聡司  長崎大学, 医歯薬学総合研究科(医学系), 講師 (10336159)
江口 正倫  長崎大学, 病院(医学系), 助教 (70585405)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺高血圧症 / 長鎖ノンコーディングRNA / バイオマーカ / 低酸素 / 肺動脈性肺高血圧
Outline of Research at the Start

肺動脈性肺高血圧症(PAH)は予後不良の病態であり、早期診断のためのバイオマーカや新しい機序の治療薬の開発が喫緊の課題である。ヒトゲノムのうちタンパク質をコードしないRNAであるノンコーディングRNAの役割が注目されており、その中で長鎖ノンコーディングRNAは、様々な病態に関与していることが明らかになりつつある。
そこで本研究では、PAH症例の血液を用いて網羅的なスクリーニングを行い、PAH発症のバイオマーカとして有用な長鎖ノンコーディングRNAを探索する。その後、同定された長鎖ノンコーディングRNAのPAH病態への関与を動物モデルで解明し、新規治療法としての可能性を検討する。

Outline of Final Research Achievements

Blood samples were collected from the pulmonary artery and left ventricle of patients with pulmonary arterial hypertension (PAH), and RNA was extracted from the obtained plasma and comprehensively analyzed for the expression levels of long non-coding (lnc) RNAs. We identified lncRNAs X and Y, whose levels were elevated in pulmonary circulation, suggesting an association with PAH. lncRNA X tended to be elevated in the pulmonary circulation of both control patients and PAH, but was higher in the blood of PAH. lncRNA Y was barely detectable in the plasma of control patients, but was detectable in the blood of PAH, and was elevated in the PAH pulmonary circulation.
These two lncRNAs are currently being validated as disease biomarkers in patients with PAH.

Academic Significance and Societal Importance of the Research Achievements

PAHは、その発症機序は未だ十分に解明されておらず、未治療のPAHの予後は極めて不良である。2000年頃より新たな治療薬が開発され、予後は改善してきているが、その効果は不十分であり、早期診断のためのバイオマーカや新しい機序の治療薬の開発が喫緊の課題である。今回の研究によりPAHの病態と関連するlncRNA XとYを同定した。今後PAHの発症機序の解明、早期診断のためのバイオマーカ、新しい治療標的となることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] The Authors' Reply to "Efficacy and Feasibility of Edoxaban Therapy without Prior Parenteral Anticoagulants in Patients with Venous Thromboembolism"2024

    • Author(s)
      Ueno Yuki、Ikeda Satoshi、Motokawa Tetsufumi、Honda Tomohiro、Kurobe Masaya、Akashi Ryohei、Yonekura Tsuyoshi、Yoshimuta Tsuyoshi、Eguchi Masamichi、Kawano Hiroaki、Maemura Koji
    • Journal Title

      Internal Medicine

      Volume: 63 Issue: 21 Pages: 3015-3016

    • DOI

      10.2169/internalmedicine.3509-24

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2024-11-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-world Safety and Effectiveness of Edoxaban in Patients with Venous Thromboembolism with or without Preceding Parenteral Anticoagulants: A Single-center Retrospective Study2024

    • Author(s)
      Ueno Yuki、Ikeda Satoshi、Motokawa Tetsufumi、Honda Tomohiro、Kurobe Masaya、Akashi Ryohei、Yonekura Tsuyoshi、Yoshimuta Tsuyoshi、Eguchi Masamichi、Kawano Hiroaki、Maemura Koji
    • Journal Title

      Internal Medicine

      Volume: 63 Issue: 13 Pages: 1845-1853

    • DOI

      10.2169/internalmedicine.2524-23

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2024-07-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Right Ventricular Dyssynchrony in Patients With Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension2022

    • Author(s)
      Yamagata Yuki、Ikeda Satoshi、Kojima Sanae、Ueno Yuki、Nakata Tomoo、Koga Seiji、Ohno Chikara、Yonekura Tsuyoshi、Yoshimuta Tsuyoshi、Minami Takako、Kawano Hiroaki、Maemura Koji
    • Journal Title

      Circulation Journal

      Volume: 86 Issue: 6 Pages: 936-944

    • DOI

      10.1253/circj.CJ-21-0849

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2022-05-25
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Living Environment Factors on Quality of Life in Patients With Chronic Thromboembolic Pulmonary Hypertension After Completion of Balloon Pulmonary Angioplasty ― A Cross-Sectional Study ―2021

    • Author(s)
      Morimoto Y, Ikeda S, Yamagata Y, Kozu R, Kawano H, Maemura K
    • Journal Title

      Circulation Reports

      Volume: 3 Issue: 5 Pages: 279-285

    • DOI

      10.1253/circrep.CR-20-0128

    • NAID

      130008036868

    • ISSN
      2434-0790
    • Year and Date
      2021-05-10
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum soluble Klotho is inversely related to coronary artery calcification assessed by intravascular ultrasound in patients with stable coronary artery disease2021

    • Author(s)
      Koga Seiji、Ikeda Satoshi、Akashi Ryohei、Yonekura Tsuyoshi、Kawano Hiroaki、Maemura Koji
    • Journal Title

      Journal of Cardiology

      Volume: 77 Issue: 6 Pages: 583-589

    • DOI

      10.1016/j.jjcc.2020.11.014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] The effectiveness of Esaxerenone on pulmonary arterial hypertension via impairing the ROS generation2023

    • Author(s)
      Masamichi Eguchi, Satoshi Ikeda, Tomohiro Honda, Yuki Ueno, Hiroki Kawano, Koji Maemura
    • Organizer
      第7回日本循環器学会基礎研究フォーラム(BCVR)
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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