• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The role of selective autophagy for the degradation of inflammasome in the progression of heart failure

Research Project

Project/Area Number 17K09570
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Yasuhiro Maejima  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40401393)

Co-Investigator(Kenkyū-buntansha) 小西 正則  東京医科歯科大学, 医学部附属病院, 助教 (70792018)
磯部 光章  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (80176263)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords心不全 / インフラマソーム / オートファジー
Outline of Final Research Achievements

The aim of this study is to establish a novel target of heart failure therapy by elucidating the role of selective autophagy that degrade inflammasome in the hearts. We found that suppression of autophagy machinery enhances accumulation of inflammasome in cardiomyocytes, thereby abrogating cardiac function in response to pressure overload in the hearts of the mice. We also demonstrated that there is the physically interaction between TRIM20 and NLRP3. In addition, we have shown that knockdown of TRIM20 enhances inflammasome activity in cardiomyocytes by suppressing selective autophagy for the degradation of inflammasome. Thus, we concluded that selective autophagy for the degradation of inflammasome would be a possible target for establishing novel therapeutic strategy against heart failure.

Academic Significance and Societal Importance of the Research Achievements

今回の申請研究では、培養心筋細胞を用いたin vitro実験ならびに実験的心筋梗塞モデルを用いて、心不全の病態において微細なタンパク複合体を特異的に分解する選択的オートファジーが関与しているのかどうかと、この選択的オートファジーの制御系が心不全の病態ではどのような影響を受けるのかについて明らかにした。特に、インフラマソームを特異的に分解する選択的オートファジーの分子機序を明らかにし、このメカニズムの破綻がインフラマソームの機能亢進を惹起して心不全の病態を悪化させているのかどうかを明らかにし、新規の心不全治療法の開発につながるような知見を見いだせた点に意義があると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] The critical roles of protein quality control systems in the pathogenesis of heart failure2020

    • Author(s)
      Maejima Yasuhiro
    • Journal Title

      Journal of Cardiology

      Volume: 75 Issue: 3 Pages: 219-227

    • DOI

      10.1016/j.jjcc.2019.09.019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SGLT2 Inhibitors Play a Salutary Role in Heart Failure via Modulation of the Mitochondrial Function2020

    • Author(s)
      Maejima Yasuhiro
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 6 Pages: 186-186

    • DOI

      10.3389/fcvm.2019.00186

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia.2019

    • Author(s)
      Saito T, Nah J, Oka SI, Mukai R, Monden Y, Maejima Y, Ikeda Yoshiyuki, Sciarretta S, Liu T, Li H, Baljinnyam E, Fraidenraich D, Fritzky L, Zhai P, Ichinose S, Isobe M, Hsu CP, Kundu M, Sadoshima J.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 129 Issue: 2 Pages: 802-819

    • DOI

      10.1172/jci122035

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-Nucleotide Polymorphism of the MLX Gene Is Associated With Takayasu Arteritis2018

    • Author(s)
      Tamura Natsuko、Maejima Yasuhiro、Matsumura Takayoshi、Vega Rick B.、Amiya Eisuke、Ito Yusuke、Shiheido-Watanabe Yuka、Ashikaga Takashi、Komuro Issei、Kelly Daniel P.、Hirao Kenzo、Isobe Mitsuaki
    • Journal Title

      Circulation: Genomic and Precision Medicine

      Volume: 11 Issue: 10

    • DOI

      10.1161/circgen.118.002296

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synergistic effects of HMG-CoA reductase inhibitor and angiotensin II receptor blocker on load-induced heart failure2018

    • Author(s)
      Ito Yusuke、Maejima Yasuhiro、Tamura Natsuko、Shiheido-Watanabe Yuka、Konishi Masanori、Ashikaga Takashi、Hirao Kenzo、Isobe Mitsuaki
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 5 Pages: 799-816

    • DOI

      10.1002/2211-5463.12416

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Critical role for dipeptidyl peptidase-4 activity in the pathogenesis of experimental autoimmune myocarditis.2018

    • Author(s)
      Yasuhiro Maejima, Yuka Shiheido-Watanabe, Natsuko Tamura, Yusuke Ito, Kenzo Hirao, Mitsuaki Isobe.
    • Organizer
      Heart Failure Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The single nucleotide polymorphism of MLX gene is involved in the development of Takayasu Arteritis.2018

    • Author(s)
      Yasuhiro Maejima.
    • Organizer
      The 2nd JCS Council Forum on Basic Cardiovascular Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] SGLT2 inhibitor directly protects oxidative stress-mediated cardiomyocyte injury by suppressing mitochondrial damage-mediated apoptosis .2018

    • Author(s)
      Yasuhiro Maejima, Shun Nakagama, Yuka Shiheido-Watanabe, Yusuke Ito, Natsuko Tamura, Kenzo Hirao, Mitsuaki Isobe.
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The critical role of protein quality control against heart failure.2018

    • Author(s)
      Yasuhiro Maejima.
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 血液凝固第X因子による動脈硬化進展作用の機序の解明.2018

    • Author(s)
      前嶋康浩.
    • Organizer
      第4回Pan-Pacific Primary Angioplasty Conference
    • Related Report
      2018 Research-status Report
    • Invited

URL: 

Published: 2017-04-28   Modified: 2022-12-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi