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2021 Fiscal Year Annual Research Report

Analysis for a role of vascular senescence in age-related disease

Research Project

Project/Area Number 19K08502
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

池田 宏二  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90423871)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywords老化 / 血管内皮細胞 / 老化関連疾患 / 加齢 / 健康長寿
Outline of Annual Research Achievements

昨年度までの研究で私達は血管内皮細胞老化がSASPを介して脂肪細胞の早期老化を誘導し、その結果、脂肪機能異常から全身の代謝異常を引き起こすことを明らかとした。一方、高齢者では心血管疾患が生命予後のみならず健康寿命にも大きな影響を与えることが知られている。心血管疾患の原因は血管の動脈硬化であり、血管内皮細胞は動脈硬化の進展においても重要な役割を果たしている。そこで今年度は血管内皮細胞老化が動脈硬化の発症・進展に及ぼす影響について解析を行なった。ApoE-KOマウスと私達が作出した血管内皮特異的老化マウスを交配し、血管内皮細胞だけが老化した動脈硬化モデルマウスを作成した。これらマウスに高コレステロール食を与えて動脈硬化の進展を評価した。その結果、血管内皮が老化したマウスでは早期(高コレステロール食負荷2週間)から動脈硬化巣の形成が促進されており、後期(高コレステロール食負荷8週間)になると粥腫の不安定化を増悪させることがわかった。血管内皮細胞老化が動脈硬化を増悪させるメカニズムの解析を進めた結果、老化血管内皮細胞ではえ炎症刺激時のNF-kBシグナルが著明に亢進しており、その結果、VCAM-1などの接着因子の発現が強く誘導され、単球の接着が促進されることが明らかとなった。更にNF-kBシグナル亢進には老化に伴うepigeneticな変化が関わっていることを見出した。血管内皮細胞の老化は老化関連疾患の発症に非常に強く関わっており、血管内皮細胞老化の予防は健康長寿に繋がる治療戦略として有望である。

  • Research Products

    (11 results)

All 2022 2021

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] ChGn-2 plays a cardioprotective role in heart failure caused by acute pressure overload2021

    • Author(s)
      Haryono A, Koji Ikeda, Nugroho DB, Ogata T, Tsuji Y, Matoba S, Moriwaki K, Kitagawa H, Igarashi M, Hirata KI, Emoto N
    • Journal Title

      J Am Heart Assoc

      Volume: - Pages: e023401-

    • DOI

      10.1161/JAHA.121.023401

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GPNMB plays a protective role against obesity-related metabolic disorders by reducing macrophage inflammatory capacity2021

    • Author(s)
      Prabata A, Ikeda K, Rahardini EP, Hirata K-I, Emoto N
    • Journal Title

      J Biol Chem

      Volume: 297 Pages: 101232-

    • DOI

      10.1016/j.jbc.2021.101232

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis2021

    • Author(s)
      Honda S, Ikeda K, Urata R, Yamazaki E, Emoto N, Matoba S
    • Journal Title

      Sci Rep

      Volume: 11 Pages: 14608-

    • DOI

      10.1038/s41598-021-94097-5

    • Peer Reviewed / Open Access
  • [Presentation] Endothelial cell senescence in aging and disease2022

    • Author(s)
      Koji Ikeda
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Invited
  • [Presentation] Chondroitin sulfate N-acetylgalactosaminyltransferase-2 plays a protective role in pressure overload-induced cardiac remodeling and heart failure2022

    • Author(s)
      Daisuke Ueno, Koji Ikeda
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
  • [Presentation] Chondroitin sulfate N-acetylgalactosaminyltransferase-2 plays a protective role in pressure overload-induced cardiac remodeling and heart failure2021

    • Author(s)
      Andreas Haryono, Koji Ikeda
    • Organizer
      The 5th JCS Council Forum on Basic CardioVascular Research
  • [Presentation] GPNMB is crucially involved in the crosstalk between adipocyte and macrophages for protection against obesity-related metabolic disorders2021

    • Author(s)
      Adam Prabata, Koji Ikeda
    • Organizer
      The 5th JCS Council Forum on Basic CardioVascular Research
  • [Presentation] Senescent Endothelial Cells Exacerbate Pulmonary Hypertension through Notch-mediated Juxtacrine Interaction with Pulmonary Artery Smooth Muscle Cell2021

    • Author(s)
      Risa Ramadhiani, Koji Ikeda
    • Organizer
      European Society of Cardiology (ESC) Congress
    • Int'l Joint Research
  • [Presentation] Chondroitin sulfate n-acetylgalactosaminyltransferase-2 (ChGn-2) plays a significant role in cardiac remodeling and heart failure following pressure overload2021

    • Author(s)
      Andreas Haryono, Koji Ikeda
    • Organizer
      European Society of Cardiology (ESC) Congress
    • Int'l Joint Research
  • [Presentation] GPNMB Protects Against Obesity-related Metabolic Disorders by Attenuating Macrophage-derived Inflammation in White Adipose Tissue through CD44 Receptor-dependent Mechanism2021

    • Author(s)
      Adam Prabata, Koji Ikeda
    • Organizer
      European Society of Cardiology (ESC) Congress
    • Int'l Joint Research
  • [Presentation] Endothelial Cells Senescence Exacerbates Pulmonary Hypertension Through Notch-Induced Pulmonary Arterial Smooth Muscle Cells Proliferation and Migration2021

    • Author(s)
      Risa Ramadhiani, Koji Ikeda
    • Organizer
      American Heart Association (AHA) Scientific Meeting
    • Int'l Joint Research

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Published: 2022-12-28  

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