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

Significance of heart-bone marrow coupling in heart failure: epigenetic regulation of cardiac macrophages

Research Project

Project/Area Number 20K17088
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionFukushima Medical University

Principal Investigator

Wada Kento  福島県立医科大学, 医学部, 助手 (10865695)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords心不全 / DNAメチル化 / エピジェネティクス / 心臓マクロファージ / クローン造血 / マクロファージ
Outline of Research at the Start

本研究では、エピジェネティクスとしてのDNAメチル化に着目して、マウス心肥大・心不全モデルを用いて、心臓マクロファージにおけるDNAメチル化のダイナミクスの意義について明らかにする。また健常人の中で、血液細胞にDNMT3aをはじめとするエピジェネティクス関連遺伝子変異が認められ、これが心血管疾患のリスクであることが報告されている。骨髄由来血液細胞のDNAメチル化異常が心不全の病態に関与することが示唆されており、マクロファージ特異的DNMT3aノックアウトマウスモデルを用いて、のDNAメチル化異常の病的意義を明らかにすることで、これらが心不全の新たな治療ターゲットとなるか検討する。

Outline of Final Research Achievements

In this study, macrophages were isolated from cardiac tissue by FACS to examine DNA methylation patterns in a mouse model of cardiac hypertrophy and heart failure. To clarify the significance of bone marrow-derived macrophages, a comprehensive analysis of DNA methylation was performed by bisulfite sequencing in bone marrow-derived macrophages that were cultured and differentiated into macrophages in ex vivo. We found multiple differentially methylated regions in epigenetically related A-mouse bone marrow-derived macrophages and wild-type bone marrow-derived macrophages, suggesting that these regions may influence the differences in immune responses, which requires further investigation.

Academic Significance and Societal Importance of the Research Achievements

エピジェネティクスは、DNAの塩基配列によらない遺伝子発現を制御・伝達するシステムであり、様々な疾患と関連する。心不全は、環境要因と遺伝的素因が複雑に影響して発症するが、エピジェネティクスは制御可能なターゲットと考えられる。本研究では、マクロファージを主体とする骨髄由来免疫細胞のエピジェネティクスに着目することで、拡張性心不全や難治性の心筋炎に対する新しいメカニズムの解明に貢献するものと考えている。さらには、近年のトピックスである「クローン性造血」においても、造血幹細胞レベルでのDNAメチル化異常が心不全の病態に関与しているかについても今後検討し臨床での治療に貢献しうることが期待できる。

Report

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

    (5 results)

All 2021

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils2021

    • Author(s)
      Kimishima Yusuke、Misaka Tomofumi、Yokokawa Tetsuro、Wada Kento、Ueda Koki、Sugimoto Koichi、Minakawa Keiji、Nakazato Kazuhiko、Ishida Takafumi、Oshima Motohiko、Koide Shuhei、Shide Kotaro、Shimoda Kazuya、Iwama Atsushi、Ikeda Kazuhiko、Takeishi Yasuchika
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 6177-6177

    • DOI

      10.1038/s41467-021-26435-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clonal Hematopoiesis and JAK2V617F Mutations in Patients With Cardiovascular Disease2021

    • Author(s)
      Yokokawa Tetsuro、Misaka Tomofumi、Kimishima Yusuke、Wada Kento、Minakawa Keiji、Kaneshiro Takashi、Yoshihisa Akiomi、Ikeda Kazuhiko、Takeishi Yasuchika
    • Journal Title

      JACC: CardioOncology

      Volume: 3 Issue: 1 Pages: 134-136

    • DOI

      10.1016/j.jaccao.2021.01.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood-based epigenetic markers of FKBP5 gene methylation in patients with dilated cardiomyopathy.2021

    • Author(s)
      Wada K, Misaka T, Yokokawa T, Kimishima Y, Kaneshiro T, Oikawa M, Yoshihisa A, Takeishi Y.
    • Journal Title

      Journal of American Heart Association

      Volume: 10 Issue: 21

    • DOI

      10.1161/jaha.121.021101

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Blood-based epigenetic markers of FKBP5 gene methylation in patients with dilated cardiomyopathy.2021

    • Author(s)
      Wada K, Misaka T, Yokokawa T, Kimishima Y, Kaneshiro T, Oikawa M, Yoshihisa A, Takeishi Y.
    • Organizer
      Cardiovascular and Metabolic Week 2021: The 38th Annual Scientific Meeting of the Japanese Section of the International Society for Heart Research (ISHR)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Blood-based epigenetic markers of FKBP5 gene methylation in patients with dilated cardiomyopathy.2021

    • Author(s)
      Wada K, Misaka T, Yokokawa T, Kimishima Y, Kaneshiro T, Oikawa M, Yoshihisa A, Takeishi Y.
    • Organizer
      American Heart Association Scientific Sessions 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi