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The roles of smooth muscle cell autophagy

Research Project

Project/Area Number 16K01833
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionJuntendo University

Principal Investigator

Mita Tomoya  順天堂大学, 医学部, 准教授 (90532557)

Research Collaborator OSONOI yusuke  
MASUYAMA atsushi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsオートファジー / 平滑筋細胞 / 動脈硬化 / 細胞死 / 細胞老化 / プラーク破綻 / 血管平滑筋細胞 / 動脈瘤 / 血管平滑筋 / 大動脈瘤
Outline of Final Research Achievements

Defective autophagy has been implicated in various human diseases, including cardiovascular diseases. In this study, we aimed to elucidate the role of autophagy in vascular smooth muscle cells (SMCs) on atherosclerosis.SMCs cultured from mice with SMC-specific deletion of the essential autophagy gene atg7 (Atg7cKO) by 7-ketocholestrerol exposure showed enhanced apoptotic cell death and cellular senescence. Atg7cKO mice crossed with Apoe-deficient mice showed a reduced survival rate, increased plaque area, and aneurysm formation. In addition, we investigated the role of autophagy in SMCs on plaque instability in vivo. To generate a mouse model of plaque instability, we conducted to form a tandem stenosis in the carotid artery of Atg7cKO:apoeKO mice. Our data suggest that defective autophagy in SMCs enhances plaque instability and the risk of plaque rupture.Thus,we suggest that activation of SMCs autophagy may be a new therapeutic target to reduce cardiovascular disease.

Academic Significance and Societal Importance of the Research Achievements

全世界において心血管イベント抑制は重要な課題である。様々な動脈硬化の発症進展を抑制する薬が開発され、患者の生命予後は改善してきているものの十分ではないのが現状である。本研究の平滑筋細胞のオートファジーが動脈硬化抑制的に作用しているという結果は、今後、オートファジーをターゲットとした新しい動脈硬化抑制薬の開発につながる可能性があり、意義の高い研究であると考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis.2018

    • Author(s)
      Osonoi Y, Mita T, Azuma K, Nakajima K, Masuyama A, Goto H, Nishida Y, Miyatsuka T, Fujitani Y, Koike M, Mitsumata M, Watada H.
    • Journal Title

      Autophagy

      Volume: 14 Issue: 11 Pages: 1991-2006

    • DOI

      10.1080/15548627.2018.1501132

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defective autophagy in vascular smooth muscle cells enhances atherosclerotic plaque instability.2018

    • Author(s)
      Masuyama A, Mita T, Azuma K, Osonoi Y, Nakajima K, Goto H, Nishida Y, Miyatsuka T, Mitsumata M, Watada H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 505 Issue: 4 Pages: 1141-1147

    • DOI

      10.1016/j.bbrc.2018.09.192

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2016-04-21   Modified: 2020-03-30  

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