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Mechano-aging in heart failure

Research Project

Project/Area Number 19H03648
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionChiba University

Principal Investigator

Manabe Ichiro  千葉大学, 大学院医学研究院, 教授 (70359628)

Co-Investigator(Kenkyū-buntansha) 藤生 克仁  東京大学, 医学部附属病院, 特任准教授 (30422306)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsメカノバイオロジー / メカニカルストレス / 心不全 / マクロファージ / 線維芽細胞 / 心筋細胞 / 老化 / 慢性炎症
Outline of Research at the Start

心不全患者は世界的に増加している。また、心臓組織のリモデリングを背景に生じる心不全が増加しており、そのメカニズムの理解と治療法の開発は喫緊の課題である。本研究では、心臓に与えられる機械的・物理的な刺激と、加齢に伴う変化がお互いに関連し合いながら心不全をもたらすと考え、その解析から、新たな心不全のメカニズムの理解を進める。特に、細胞間の相互作用と、エピゲノムの制御に着目した研究を行う。

Outline of Final Research Achievements

The number of heart failure patients is increasing worldwide. In particular, the remodeling of cardiac tissues, such as fibrosis, is important for the development of heart failure in the elderly. The elucidation of the molecular mechanisms of heart failure from a new perspective and the development of therapeutic methods are needed. We hypothesized that the responsive mechanisms to mechanical stress and aging are linked at various levels. We coined the interaction between mechanical stress response and aging as "mechano-aging" and conducted research with the aim of elucidating a new mechanism for the onset of heart failure. As a result, we identified changes in cardiac tissue macrophages that are shared between mechanical stress and aging, and the mediators that modulate cardiac homeostasis by these changes.

Academic Significance and Societal Importance of the Research Achievements

従来の心不全の研究は主に心筋細胞に着目していたが、急増している高齢者の心不全では心臓組織のリモデリングが特徴であり、心筋細胞に加えて、線維芽細胞や内皮細胞、マクロファージを始めとする免疫細胞の相互作用によって形成されると考えられる。本研究では、メカニカルストレスと加齢で共通してみられる心臓の変化について、特に細胞間のコミュニケーションに着目して検討を進めた。その結果、心臓組織マクロファージの変化を見いだし、心臓恒常性の変調をもたらす可能性が高いマクロファージ由来のメディエータを同定した。マクロファージの変化や同定した分子の解析を進めることによって、新たな診断治療標的を同定できると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (34 results)

All 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (26 results) (of which Int'l Joint Research: 6 results,  Invited: 26 results) Remarks (3 results)

  • [Journal Article] Nerve?macrophage interactions in cardiovascular disease2021

    • Author(s)
      Fujiu Katsuhito、Manabe Ichiro
    • Journal Title

      International Immunology

      Volume: 34 Issue: 2 Pages: 81-95

    • DOI

      10.1093/intimm/dxab036

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiac macrophages prevent sudden death during heart stress.2021

    • Author(s)
      Sugita J, Fujiu K, Nakayama Y, Matsubara T, Matsuda J, Oshima T, Liu Y, Maru Y, Hasumi E, Kojima T, Seno H, Asano K, Ishijima A, Tomii N, Yamazaki M, Kudo F, Sakuma I, Nagai R, Manabe I, Komuro I.
    • Journal Title

      Nat Commun.

      Volume: 12(1) Issue: 1 Pages: 1910-1910

    • DOI

      10.1038/s41467-021-22178-0

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy2021

    • Author(s)
      Liu L, Koike H, Ono T, Hayashi S, Kudo F, Kaneda A, Kagechika H, Manabe I, Nakashima T, Oishi, Y.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 118 Issue: 35

    • DOI

      10.1073/pnas.2102895118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation2020

    • Author(s)
      Nakayama Yukiteru、Fujiu Katsuhito、Yuki Ryuzaburo、Oishi Yumiko、Morioka Masaki Suimye、Isagawa Takayuki、Matsuda Jun、Oshima Tsukasa、Matsubara Takumi、Sugita Junichi、Kudo Fujimi、Kaneda Atsushi、Endo Yusuke、Nakayama Toshinori、Nagai Ryozo、Komuro Issei、Manabe Ichiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 25 Pages: 14365-14375

    • DOI

      10.1073/pnas.2005924117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organ system crosstalk in cardiometabolic disease in the age of multimoribidity2020

    • Author(s)
      Oishi Y, Manabe I
    • Journal Title

      Frontiers in Cardiovascluar Medicine

      Volume: - Pages: 64-64

    • DOI

      10.3389/fcvm.2020.00064

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Macrophage diversity in age-associated cardiovascular disease2022

    • Author(s)
      眞鍋一郎
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Organ crosstalk and macrophage in cardiovasdular homeostasis and multimorbidity2022

    • Author(s)
      眞鍋一郎
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 循環・神経・免疫系の連携による恒常性の維持と破綻2021

    • Author(s)
      眞鍋一郎
    • Organizer
      第43回日本血栓止血学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Neuro-Immune-Metabolic Regulation of Cardiac Homeostasis and Disease2021

    • Author(s)
      Ichiro Manabe
    • Organizer
      上原国際シンポジウム2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞多様性と心血管疾患2021

    • Author(s)
      眞鍋一郎
    • Organizer
      第39回日本内分泌学会 内分泌代謝学サマーセミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Immunometabolic control in macrophages2021

    • Author(s)
      Ichiro Manabe
    • Organizer
      The 10th International Congress on Lipid & Atherosclerosis
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心不全における造血-マクロファージコンティニュアム2021

    • Author(s)
      眞鍋一郎
    • Organizer
      生体機能と創薬シンポジウム2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 循環・代謝・神経・免疫系の連携による恒常性維持と心血管疾患2021

    • Author(s)
      眞鍋一郎
    • Organizer
      第53回日本動脈硬化学会総会・学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 心―脳ー腎連関2021

    • Author(s)
      眞鍋一郎
    • Organizer
      第74回日本自律神経学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Immunometabolic Regulation of Macrophages in Cardiovascular Disease2021

    • Author(s)
      Ichiro Manabe
    • Organizer
      The 19th International Symposium on Atherosclerosis
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Macrophage diversity in the organ crosstalk and multimorbidity2021

    • Author(s)
      Ichiro Manabe
    • Organizer
      The 19th International Symposium on Atherosclerosis
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Macrophage diversity in cardiovascular homeostasis and multimorbidity2021

    • Author(s)
      眞鍋一郎
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Macrophages in the cardiovascular organ crosstalk and mulbimorbidity2021

    • Author(s)
      Manabe I
    • Organizer
      International Society for Applied Cardiovascular Biology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Macrophages and organ crosstalk in homeostasis and multimorbidity2021

    • Author(s)
      Manabe I
    • Organizer
      第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Age-associated alterations in macrophage populations and functions modulate cardiac homeostasis and promote remodeling.2021

    • Author(s)
      Manabe I
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The hematopoietic continuum and macrophages in heart failure and multimorbidity2021

    • Author(s)
      Manabe I
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Functional Diversity and modulation of macrophaes in organ crosstalk and cardiovascular disease.2020

    • Author(s)
      Manabe I
    • Organizer
      International Vascular Biology Meeting 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 5.Macrophages and Organ System Crosstalks in Cardiac Homeostasis and Disease2019

    • Author(s)
      Manabe I
    • Organizer
      BCVR2019: The 3rd JCS Council Forum of Basic Cardiovascular Research
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 老化関連疾患における組織マクロファージ2019

    • Author(s)
      真鍋一郎
    • Organizer
      第16回脳心血管抗加齢研究会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Macrophages in cardiac biology and pathobiology2019

    • Author(s)
      真鍋一郎
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 肥満による臓器システム関連系の変調と心血管代謝疾患2019

    • Author(s)
      真鍋一郎
    • Organizer
      第40回日本肥満学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 心臓組織マクロファージによるストレス応答と破綻2019

    • Author(s)
      真鍋一郎
    • Organizer
      第92回日本生化学大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 免疫-代謝-神経連関とマクロファージによるストレス応答と修復2019

    • Author(s)
      真鍋一郎
    • Organizer
      第40回日本・炎症再生医学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 組織マクロファージと臓器連関によるストレス応答機構2019

    • Author(s)
      真鍋一郎
    • Organizer
      第28回日本Cell Death学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Macrophages in Cardiac Physiology and Disease2019

    • Author(s)
      Manabe I
    • Organizer
      The 26th International Symposium on Molecular Cell Biology of Macrophages
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 心腎脳連関と恒常性維持機構2019

    • Author(s)
      真鍋一郎
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/manabe

    • Related Report
      2021 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/manabe

    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/manabe

    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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