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Effect of periodontal infection on cardiac hypertrophy through dysregulation of autophagy and its mechanism.

Research Project

Project/Area Number 19K18985
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Shiheido Yuka  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (60791853)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords歯周病原細菌 / オートファジー / 歯周病 / 心肥大
Outline of Research at the Start

細胞内分解機構であるオートファジーの制御異常が様々な疾患に関与することが報告され、心筋における細胞内タンパクの品質保持や細胞内に侵入する病原体の除去にもオートファジーが機能していることが明らかとなっている。申請者は以前に歯周病原細菌Porphyromonas gingivalisが感染している梗塞心筋では心破裂が頻発し、その原因が心筋細胞におけるミトコンドリア選択的オートファジーの抑制にあることを報告している。これらよりオートファジー制御異常が歯周病と心血管疾患の関わりを解明する鍵を握っていると考え、歯周病原細菌の感染がオートファジー制御異常を介して心肥大に与える影響とその機序を解明していく。

Outline of Final Research Achievements

An association between periodontal disease and cardiovascular disease has been suggested, but the detailed mechanism remains unclear. Recently, dysregulation of autophagy, an intracellular degradation mechanism, has been reported to be involved in several systemic diseases. In particular, autophagy has been shown to play an important role in maintaining the homeostasis of cardiomyocytes, which are non-dividing cells. Based on the results of previous studies, the applicant has been investigating the possibility that dysregulation of autophagy may hold the key to elucidating the relationship between periodontal disease and cardiovascular disease.
This year, we were able to synthesize the results of in vivo and in vitro studies obtained to date.

Academic Significance and Societal Importance of the Research Achievements

本研究よりオートファジー制御機構が歯周病と心血管疾患とを結びつける因子である可能性を一層高めることができた。さらなる研究を進めることで世界に先駆けてオートファジー制御機構をターゲットとした新規治療法の確立や創薬開発へと発展させることができると考える。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (8 results)

  • [Journal Article] Association between periodontal disease and pericardial adipose tissue in patients with cardiovascular disease2023

    • Author(s)
      Kanno Yoshinori、Yonetsu Taishi、Aoyama Norio、Shiheido-Watanabe Yuka、Yoshikawa Hiroshi、Ohmori Mari、Tashiro Akira、Niida Takayuki、Matsuda Yuji、Araki Makoto、Usui Eisuke、Hada Hiroto、Umemoto Tomoyuki、Maejima Yasuhiro、Isobe Mitsuaki、Iwata Takanori、Sasano Tetsuo
    • Journal Title

      American Heart Journal Plus: Cardiology Research and Practice

      Volume: 30 Pages: 100298-100298

    • DOI

      10.1016/j.ahjo.2023.100298

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of periodontal health in cardiovascular secondary prevention: Analyses on hospitalized patients in cardiology units2023

    • Author(s)
      Hamaya Rikuta、Yonetsu Taishi、Aoyama Norio、Shiheido‐Watanabe Yuka、Tashiro Akira、Niida Takayuki、Isobe Mitsuaki、Maejima Yasuhiro、Iwata Takanori、Sasano Tetsuo
    • Journal Title

      Journal of Clinical Periodontology

      Volume: 50 Issue: 6 Pages: 708-716

    • DOI

      10.1111/jcpe.13792

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil extracellular traps-mediated Beclin-1 suppression aggravates atherosclerosis by inhibiting macrophage autophagy2022

    • Author(s)
      Sano Masataka、Maejima Yasuhiro、Nakagama Shun、Shiheido-Watanabe Yuka、Tamura Natsuko、Hirao Kenzo、Isobe Mitsuaki、Sasano Tetsuo
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 876147-876147

    • DOI

      10.3389/fcell.2022.876147

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rivaroxaban, a Direct Oral Factor Xa Inhibitor, Attenuates Atherosclerosis by Alleviating Factor Xa-PAR2-Mediated Autophagy Suppression.2021

    • Author(s)
      Ito Y, Maejima Y, Nakagama S, Shiheido-Watanabe Y, Tamura N, Sasano T.
    • Journal Title

      JACC Basic Transl Sci.

      Volume: 6 Issue: 12 Pages: 964-980

    • DOI

      10.1016/j.jacbts.2021.09.010

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Periodontal Disease on Long-Term Outcomes After Percutaneous Coronary Intervention for De Novo Coronary Lesions in Non-Smokers.2021

    • Author(s)
      Fukushima T, Yonetsu T, Aoyama N, Tashiro A, Niida T, Shiheido-Watanabe Y, Maejima Y, Isobe M, Iwata T, Sasano T.
    • Journal Title

      Circ J.

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma apolipopotein C-2 elevation is associated with Takayasu arteritis2021

    • Author(s)
      Tamura N, Maejima Y, Shiheido-Watanabe Y, Nakagama S, Isobe M, Sasano T
    • Journal Title

      Sci Rep

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis2021

    • Author(s)
      Shiheido-Watanabe Y, Maejima Y, Kasama T, Tamura N, Nakagama S, Ito Y, Hirao K, Isobe M, Sasano T
    • Journal Title

      JACC Basic Transl Sci

      Volume: 6 Pages: 527-542

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] SNARE Proteins are Critical Factors for Periodontal Pathogens-mediated Aggravation of Myocardial Infarction2022

    • Author(s)
      Yuka Shiheido-Watanabe, Yasuhiro Maejima, Natsuko Tamura, Shun Nakagama, Tetsuro Sasano.
    • Organizer
      第86回 日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 歯周病原細菌感染がオートファジー制御異常を介して心筋梗塞マウスモデルに与える影響とその分子機序の解明2022

    • Author(s)
      渡辺(始平堂)由佳、前嶋康浩、中釜瞬、田村夏子、范沁涛、笹野哲郎.
    • Organizer
      第10回 Heart Science Club
    • Related Report
      2022 Annual Research Report
  • [Presentation] SNARE Proteins are Critical Factors for Periodontal Pathogen-mediated Aggravation of Myocardial Infarction2022

    • Author(s)
      Yuka Shiheido-Watanabe, Yasuhiro Maejima, Natsuko Tamura, Shun Nakagama, Tetsuo Sasano
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Association of Periodontitis with Clinical Outcomes after Catheter Ablation for Paroxysmal Atrial Fibrillation2022

    • Author(s)
      Akira Tashiro, Taishi Yonetsu, Norio Aoyama, Yuka Shiheido-Watanabe, Takayuki Niida, Mitsuaki Isobe, Takanori Iwata, Tetsuo Sasano.
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周病菌の感染が心筋梗塞マウスモデルの病態に及ぼす影響とその分子機序の解明2021

    • Author(s)
      渡辺(始平堂)由佳、前嶋康浩、田村夏子、中釜瞬、米津太志、笹野哲郎
    • Organizer
      第262回日本循環器学会関東甲信越地方会
    • Related Report
      2021 Research-status Report
  • [Presentation] Invasion of a periodontal pathogen, Porphyromonas gingivalis, in myocardium causes dysregulation of autophagic machinery through abrogating function of VAMP82020

    • Author(s)
      Yuka Shiheido-Watanabe, Yasuhiro Maejima, Natsuko Tamura, Shun Nakagama, Tetsuo Sasano
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] MLX Mutation is Associated with Aggravation of Periaortic Brown Adipose Tissue Inflammation-mediated Large Vessel Vasculitis in Mice.2020

    • Author(s)
      Natsuko Tamura, Yasuhiro Maejima, Yuka Watanabe, Shun Nakagama, Mitsuaki Isobe, Tetsuo Sasano.
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Porphyromonas gingivalis , a periodontal pathogen, dysregulates autophagy by abrogating autophagosomelysosome fusion in cardiomyocytes2019

    • Author(s)
      Yuka Shiheido-Watanabe, Yasuhiro Maejima, Natsuko Tamura, Shun Nakagama, Tetsuo Sasano
    • Organizer
      第3回日本循環器学会基礎研究フォーラム
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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