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Elucidation of pathomechanisms causing fibrosis of sinus node and development of treatment for prevention of progression

Research Project

Project/Area Number 21K06770
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionOita University

Principal Investigator

SHINOHARA TETSUJI  大分大学, 医学部, 講師 (60457629)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords心房筋線維化 / 洞結節機能障害 / 心房細動 / 洞房結節 / 心外膜脂肪 / 心外膜脂肪組織
Outline of Research at the Start

これまで肥満患者における洞結節機能障害に関する詳細なメカニズムの報告はなく、このメカニズムにIfチャネルを含めたリズム発生に関わる因子のリモデリングが関与している可能性を研究することは斬新かつ独創的である。洞結節リモデリングのメカニズムを解明し、洞不全症候群患者への新しい治療法の開発に繋げていくことができる。

Outline of Final Research Achievements

It is believed that the membrane clock, which is centered on If channels, and the Ca2+ clock, which is mediated by spontaneous Ca2+ release from the sarcoplasmic reticulum, function in a complementary manner to generate sinus rhythm. Our study confirms that patients with notched P waves, which are seen on 12-lead ECG and considered indicative of myocardial fibrosis, are more likely to have early recurrence of atrial fibrillation (AF) after electrical cardioversion. This finding suggests that atrial fibrosis is involved in the development of AF in real-life clinical practice. In addition, epicardial adipose tissue induced fibrosis of sinus node cells and surrounding atrial myocytes, suggesting that this is involved in the induction of AF.

Academic Significance and Societal Importance of the Research Achievements

肥満およびメタボリックシンドローム患者の増大が引き起こす合併症は解決すべき課題となっている。洞不全症候群および心房細動などのリズム異常を合併することが多く、そのメカニズムとして洞結節細胞の線維化およびリモデリングなどの関与が示唆される。今回の我々の研究によって心房筋組織の線維化および興奮伝導障害が洞結節機能障害、および心房細動の出現に関与していることが確認された。このことは、心房筋線維化の原因となりうる肥満およびメタボリックシンドロームがリズムに及ぼす影響を証明することができたと考えられる。今後さらにそのメカニズムを明らかにしていくことで、新しい治療方法の開発に繋げていくことができる。

Report

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

    (7 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 1 results)

  • [Journal Article] Quality of epicardial adipose tissue predicts major adverse cerebral and cardiovascular events following transcatheter aortic valve implantation2024

    • Author(s)
      Sato Takaaki、Yufu Kunio、Yamasaki Hirochika、Harada Taisuke、Yamauchi Shuichiro、Ishii Yumi、Fukuda Tomoko、Kawashima Takayuki、Shuto Takashi、Akioka Hidefumi、Shinohara Tetsuji、Teshima Yasushi、Wada Tomoyuki、Miyamoto Shinji、Takahashi Naohiko
    • Journal Title

      Heart and Vessels

      Volume: 16 Issue: 7 Pages: 51905-51905

    • DOI

      10.1007/s00380-024-02374-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study.2023

    • Author(s)
      Miyoshi M, Abe I, Kodama N, Zhan Y, Kira S, Ishii Y, Harada T, Takano M, Takahashi M, Sato H, Tawara K, Kondo H, Fukui A, Fukuda T, Akioka H, Shinohara T, Teshima Y, Yufu K, Nakagawa M, Daa T, Shimada T, Takahashi N.
    • Journal Title

      Sci Rep.

      Volume: Jun 17;13(1): Issue: 1 Pages: 9828-9828

    • DOI

      10.1038/s41598-023-36677-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vagal response is involved in the occurrence of ventricular fibrillation in patients with early repolarization syndrome2023

    • Author(s)
      Fukuda Tomoko、Shinohara Tetsuji、Yonezu Keisuke、Mitarai Kazuki、Hirota Kei、Kondo Hidekazu、Fukui Akira、Akioka Hidefumi、Teshima Yasushi、Yufu Kunio、Nakagawa Mikiko、Takahashi Naohiko
    • Journal Title

      Heart Rhythm

      Volume: 20 Issue: 6 Pages: 879-885

    • DOI

      10.1016/j.hrthm.2023.02.029

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] Relationship between the occurrence of ventricular fibrillation and autonomic nervous function in patients with Brugada syndrome and early repolarization syndrome2023

    • Author(s)
      Tetsuji Shinohara, Tomoko Fukuda, Keisuke Yonezu, Kazuki Mitarai, Kei Hirota, Hidekazu Kondo, Akira Fukui, Hidefumi Akioka, Yasushi Teshima, Kunio Yufu, Mikiko Nakagawa, Naohiko Takahashi
    • Organizer
      The 69th Annual Meeting of the Japanese Heart Rhythm Society
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Relationship between the Occurrence of Ventricular Fibrillation and Vagal Responses in Patients with Brugada Syndrome and Early Repolarization Syndrome2023

    • Author(s)
      Tetsuji Shinohara, Keisuke Yonezu, Kazuki Mitarai, Kei Hirota, Hidekazu Kondo, Akira Fukui, Hidefumi Akioka, Yasushi Teshima, Kunio Yufu, Mikiko Nakagawa, Naohiko Takahashi
    • Organizer
      The 87th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2023 Annual Research Report
  • [Presentation] Impact of the notched P wave on early recurrence of atrial fibrillation after electrical cardioversion2022

    • Author(s)
      Hirochika Yamasaki, Keisuke Yonezu, Tetsuji Shinohara, Masaki Takahashi, Nozomi Kodama, Miho Miyoshi, Kei Hirota, Ichitaro Abe, Hidekazu Kondo, Akira Fukui, Hidefumi Akioka, Yasushi Teshima, Kunio Yufu, Mikiko Nakagawa, Naohiko Takahashi
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Potential Role of Baroreflex Sensitivity in Patients with Atrial Fibrillation2022

    • Author(s)
      Miho Miyoshi、Hidekazu Kondo、Yumi Ishii、Kei Hirota、Akira Fukui、Tetsuji Shinohara、Mikiko Nakagawa、 Shinji Miyamoto、Naohiko Takahashi
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Research-status Report

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

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