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Elucidation of the new pathogenic mechanism of heart diseases due to dysfunction of tissue immune cells and development of therapeutic methods

Research Project

Project/Area Number 19K22615
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Fujiu Katsuhito  東京大学, 医学部附属病院, 特任准教授 (30422306)

Co-Investigator(Kenkyū-buntansha) 小島 敏弥  東京大学, 医学部附属病院, 助教 (30625588)
荷見 映理子  東京大学, 医学部附属病院, 特任助教 (70599547)
中山 幸輝  東京大学, 医学部附属病院, 助教 (70721885)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords心不全 / 心臓突然死 / 不整脈 / 免疫細胞 / マクロファージ
Outline of Research at the Start

心不全、心臓突然死の疾患研究は心筋細胞を中心に行われてきたが、我々は心臓マクロファージが心臓に対して保護的に働いていることを明らかにした。本研究では、さらに心臓マクロファージを含みミエロイド系細胞が心臓病発症にどのようにかかわっているかを、1細胞遺伝子発現解析、1細胞エピゲノム解析等を用いて解析し、新しい治療標的を同定する。具体的には、心臓を保護する新規細胞の同定、その細胞が分泌するタンパクの同定、さらに疾患研究として、その新保護的細胞がどのように機能低下に陥るかについて検討する。

Outline of Final Research Achievements

So far, we have found that the immune cells of the heart have the effect of helping the cardiac contraction. However, the heart has multiple functions, and the function of immune cells in the heart for these functions is not well understood. This study identified new protective effects of immune cells in the heart. In addition, we investigated how its protective role could become dysfunctional and develop heart diseases.
Here we find that the immune cells of the heart are essential for forming the normal rhythm of the heart, in addition to its protective effect on the contraction of the heart. Furthermore, although cardiac macrophages cannot exert a protective influence when they become inflammatory macrophages, we have discovered a new mechanism for converging the inflammation of cardiac macrophages.

Academic Significance and Societal Importance of the Research Achievements

心不全・心臓突然死といった心疾患は、高齢者に多く、高齢化社会の進む本邦において、増加傾向となっており、医療費の増大を生じ社会的な問題にもなっている。そのため、心不全や心臓突然死に対する解決策を開発することは喫緊の課題である。本研究では心臓内の免疫細胞に着目して、心疾患の新しい機序を解明し、新規治療法の基盤を構築する。このような研究は、健康寿命の延伸や医療費の削減に資する

Report

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

    (3 results)

All 2022 2021 2020

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] 心不全およびその併発疾患の治療法、治療剤および診断法。2022

    • Inventor(s)
      藤生 克仁,中山 幸輝,小室 一成,眞鍋 一郎
    • Industrial Property Rights Holder
      藤生 克仁,中山 幸輝,小室 一成,眞鍋 一郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas

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Published: 2019-07-04   Modified: 2023-01-30  

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