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The role of macrophagic MKL1 in the pathogenesis of atherosclerosis

Research Project

Project/Area Number 18K15060
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionAkita University (2019)
Tokyo Medical and Dental University (2018)

Principal Investigator

An Jianbo  秋田大学, 医学系研究科, 助教 (40723771)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords動脈硬化症 / MKL1 / マクロファージ / 細胞増殖 / MRTF-A / 動脈硬化 / 脂肪萎縮症
Outline of Final Research Achievements

It has been reported that promoter polymorphism of MKL1 is associated with coronary atherosclerosis. However, the contribution of MKL1 to the development of atherosclerosis remains unclear. Macrophages are known to be important mediators of atherosclerosis. In this study, it was found that MKL1 was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. To investigate the role of macrophagic MKL1 in the pathogenesis of atherosclerosis, I generated ApoE null MKL1 transgenic mice (ApoE-KO/MKL1-TgM), in which human MKL1 was specifically overexpressed in monocytes/macrophages. ApoE-KO/MKL1-TgM aggravated atherosclerosis and accumulated prominent lesional macrophages in the aortic sinus. It was also found that MKL1 promoted proliferation of macrophages and mitigated apoptosis both in vitro and in vivo due to downregulation of the expression of CDKI.

Academic Significance and Societal Importance of the Research Achievements

冠動脈硬化症の成因については、生活習慣の蓄積と同時に、遺伝的背景が発症や進展を左右することが知られており、従って、ゲノム多様性の観点から、冠動脈硬化症の形成機構を分子レベルで解明し、その知見を予防または治療に繋ぐ研究成果を提供することが、社会的にも要請されている。先行研究において、網羅的ゲノム解析から新たな冠動脈疾患関連遺伝子座としてのMKL1遺伝子多型の同定し、本研究課題において、MKL1による動脈硬化症の分子機構を明らかにすることは、とりわけ世界的にも例のない高齢化社会を迎えているわが国において、健康長寿社会を実現するために必要な研究成果である。

Report

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

    (6 results)

All 2020 2019 2018 Other

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

  • [Journal Article] MRTF-A regulates proliferation and survival properties of pro-atherogenic macrophages2019

    • Author(s)
      An J, Naruse K T, Hinohara K, Soejima Y, Sawabe M, Nakagawa Y, Kuwahara K, Kimura A.
    • Journal Title

      Journal of Molecular and cellular cardiology

      Volume: 133 Pages: 26-35

    • DOI

      10.1016/j.yjmcc.2019.05.015

    • NAID

      130007811832

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] MRTF-A regulates proliferation and survival properties of pro-atherogenic macrophages2020

    • Author(s)
      Jianbo An, Taeko Naruse, Kunihiko Hinohara, Yurie Soejima, Motoji Sawabe, Yasuaki Nakagawa, Koichiro Kuwahara, Keiji Kuba, Akinori Kimura
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MRTF-Aはマクロファージ機能を制御して動脈硬化形成に関わる2019

    • Author(s)
      安 健博、成瀬 妙子、日野原 邦彦、副島 友莉恵、沢辺 元司、中川 靖章、桑原 宏一郎、久場 敬司、木村 彰方
    • Organizer
      第29回日本循環薬理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MKL1 Affects Proliferation/Survival Property of Pro-Atherogenic Macrophages2018

    • Author(s)
      Jianbo An, Taeko K Naruse, Akinori Kimura
    • Organizer
      Vascular Discovery: From Genes to Medicine 2018 Scientific Session (ATVB/PVD 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] プレスリリース

    • URL

      http://www.tmd.ac.jp/press-release/20190605_1/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 2018年度第1回難治疾患研究所国際研究者海外派遣プログラム報告

    • URL

      http://www.tmd.ac.jp/mri/guide/program/h30/01.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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