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Role of mitochondrial respiratory function of the epicardial addipose tissue for atrial fibrillation

Research Project

Project/Area Number 22K08197
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Watanabe Masaya  北海道大学, 医学研究院, 客員研究員 (40632047)

Co-Investigator(Kenkyū-buntansha) 畑中 豊  北海道大学, 大学病院, 特任准教授 (30589924)
新宮 康栄  北海道大学, 医学研究院, 講師 (30617064)
横田 卓  北海道大学, 大学病院, 特任講師 (90374321)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心外膜脂肪 / 心房細動 / ミトコンドリア呼吸能 / ミトコンドリア
Outline of Research at the Start

近年、心臓周囲脂肪(EAT)の過剰な蓄積と心房細動との関連が報告されている。ミトコンドリアはエネルギー産生の多くを担い、ミトコンドリア機能の異常は心血管病や神経疾患などの発症に関わる。EATのミトコンドリア機能異常は、活性酸素種(ROS)の産生増加やEATの蛋白分泌プロファイルを変化させる可能性がある。しかし、心房細動の発症機序解明を目的としたEATミトコンドリア機能の解析を行った研究はこれまでに皆無である。本研究では、EATのミトコンドリア機能に着目し、「EATミトコンドリア機能低下は、アディポサイトカインの分泌異常やROSの産生増加によって心房細動基質を進展させる」という仮説の検証を行う。

Outline of Final Research Achievements

Epicardial adipose tissue samples and clinical data were collected from 53 patients. As initially hypothesized, no significant differences were observed in atrial remodeling markers or postoperative atrial fibrillation incidence between groups divided by the median of mitochondrial oxygen consumption. Adipocytokine secretion from epicardial adipose tissue was measured using immunoassays, and correlations with mitochondrial respiration per tissue weight were evaluated. Mitochondrial respiration showed a positive correlation with MCP1 and adiponectin levels. Conversely, a strong negative correlation was observed between mitochondrial respiration and adipocyte cross-sectional area, suggesting an association between mitochondrial function and adipocyte density within the tissue.

Academic Significance and Societal Importance of the Research Achievements

心臓周囲脂肪におけるミトコンドリア呼吸能が脂肪組織の形態変化や分泌機能にどのように影響するかについて、新たな知見を得ることができた。研究成果により、心房細動基質と心外膜脂肪組織との関連についての知見を加えることができた。
また、術後心房細動の発生率やその発生に関わる患者因子についても知見を加えることができた。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (7 results)

All 2025 2024 2023

All Journal Article (7 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results)

  • [Journal Article] Serum Vasoactive Intestinal Peptide as a Novel Biomarker for Low‐Voltage Areas in Patients With Atrial Fibrillation2025

    • Author(s)
      Nishino Kotaro、Temma Taro、Natsui Hiroyuki、Watanabe Masaya、Nakao Motoki、Kawasaki Masahiro、Shimano Kintaro、Kawakami Kei、Saito Shota、Koya Jiro、Tatsuta Daishiro、Koizumi Takuya、Kadosaka Takahide、Koya Taro、Tsuneta Satonori、Kamiya Kiwamu、Nagai Toshiyuki、Anzai Toshihisa
    • Journal Title

      Journal of the American Heart Association

      Volume: 14 Issue: 7

    • DOI

      10.1161/jaha.124.039192

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Inappropriate Shocks in Brugada Syndrome Patients With a Subcutaneous Implantable Cardioverter Defibrillator2025

    • Author(s)
      Watanabe Masaya、Nanbu Tadafumi、Ishidoya Yuki、Suzuki George、Yotsukura Akihiko、Yoshida Izumi、Tanaka Yoshitaka、Inoue Kazushige、Mitsuishi Junko、Kanno Tomomi、Sakurai Masayuki、Anzai Toshihisa
    • Journal Title

      Pacing and Clinical Electrophysiology

      Volume: 48 Issue: 2 Pages: 160-168

    • DOI

      10.1111/pace.15151

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial2024

    • Author(s)
      Fujiki Shinya、Watanabe Masaya、Minamino Tohru、for the EMPA ICD investigators
    • Journal Title

      Cardiovascular Diabetology

      Volume: 23 Issue: 1

    • DOI

      10.1186/s12933-024-02309-9

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Influence of epicardial adipose tissue inflammation and adipocyte size on postoperative atrial fibrillation in patients after cardiovascular surgery2024

    • Author(s)
      Natsui H、Watanabe M、Yokota T、Tsuneta S、Fumoto Y、Handa H、Shouji M、Koya J、Nishino K、Tatsuta D、Koizumi T、Kadosaka T、Nakao M、Koya T、Temma T、Ito Y、Hatanaka K、Hatanaka Y、Yasushige S、Wakasa S、Miura S、Masuda T、Nishioka N、Naraoka S、Ochi K、Kudo T、Ishikawa T、Anzai T
    • Journal Title

      Physiological Reports

      Volume: 12 Issue: 6

    • DOI

      10.14814/phy2.15957

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats2023

    • Author(s)
      Koizumi Takuya、Watanabe Masaya、Yokota Takashi、Tsuda Masumi、Handa Haruka、Koya Jiro、Nishino Kotaro、Tatsuta Daishiro、Natsui Hiroyuki、Kadosaka Takahide、Koya Taro、Nakao Motoki、Hagiwara Hikaru、Kamada Rui、Temma Taro、Tanaka Shinya、Anzai Toshihisa
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 10 Pages: 1005408-1005408

    • DOI

      10.3389/fcvm.2023.1005408

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optogenetic termination of atrial tachyarrhythmias by brief pulsed light stimulation2023

    • Author(s)
      Nakao Motoki、Watanabe Masaya、Miquerol Lucile、Natsui Hiroyuki、Koizumi Takuya、Kadosaka Takahide、Koya Taro、Hagiwara Hikaru、Kamada Rui、Temma Taro、de Vries Antoine A.F.、Anzai Toshihisa
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 178 Pages: 9-21

    • DOI

      10.1016/j.yjmcc.2023.03.006

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Empagliflozin attenuates arrhythmogenesis in diabetic cardiomyopathy by normalizing intracellular Ca handling in ventricular cardiomyocytes2023

    • Author(s)
      Kadosaka Takahide、Watanabe Masaya、Natsui Hiroyuki、Koizumi Takuya、Nakao Motoki、Koya Taro、Hagiwara Hikaru、Kamada Rui、Temma Taro、Karube Fuyuki、Fujiyama Fumino、Anzai Toshihisa
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 324 Issue: 3 Pages: H341-H354

    • DOI

      10.1152/ajpheart.00391.2022

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2022-04-19   Modified: 2026-01-16  

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