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A diagnostic approach for lethal cardiac hypertrophy based on the analysis of autophagy-lysosomal pathway

Research Project

Project/Area Number 18K17419
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionTokai University

Principal Investigator

KAKIMOTO Yu  東海大学, 医学部, 講師 (40734166)

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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords心臓性突然死 / 心肥大 / オートファジー / リソソーム / リポフスチン / カテプシン / 年齢推定 / 加齢 / 心臓
Outline of Final Research Achievements

It was revealed that myocardial lipofuscin (LF) is useful for age estimation. The amount of LF is increased in cancer but unchanged in sudden cardiac death. LF accumulation is not correlated with the amount of LC3-II or p62, which indicates that LF is not a direct biomarker for autophagy dysfunction.
The major proteasomes of lysosomes, CTSB and CTSD increased in aging, but the levels of p62、ATP synthase, andα-synuclein were unchanged. In sudden cardiac death with cardiac hypertrophy, CTSD was significantly decreased, but the levels of p62、ATP synthase, andα-synuclein were unchanged.

Academic Significance and Societal Importance of the Research Achievements

心筋のLF定量は、通常の組織標本作成と並行して行える検査であるため、身元不明者の年齢推定に役立てられる。また、本研究では癌などの慢性疾患でのLF増加が示唆されたことから死因究明にも活用できると考えらえる。
リソソームのタンパク質分解酵素については、CTSDの減少が心臓性突然死のリスクマーカーとなる可能性が示され、生理的心肥大と病的心肥大の鑑別への活用が期待される。

Report

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

    (7 results)

All 2020 2019 2018

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

  • [Journal Article] Myocardial cathepsin D is downregulated in sudden cardiac death.2020

    • Author(s)
      Kakimoto Y, Sasaki A, Niioka M, Kawabe N, Osawa M.
    • Journal Title

      PLoS One

      Volume: 15(3) Issue: 3 Pages: e0230375-e0230375

    • DOI

      10.1371/journal.pone.0230375

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myocardial lipofuscin accumulation in ageing and sudden cardiac death2019

    • Author(s)
      Article | OPEN | Published: 01 March 2019 Myocardial lipofuscin accumulation in ageing and sudden cardiac death Yu Kakimoto, Chisa Okada, Noboru Kawabe, Ayumi Sasaki, Hideo Tsukamoto, Ryoko Nagao, Motoki Osawa
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3304-3304

    • DOI

      10.1038/s41598-019-40250-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of miR-221 in sudden death with cardiac hypertrophy patients2018

    • Author(s)
      Yu Kakimoto, Masayuki Tanaka, Hideki Hayashi, Keiko Yokoyama, Motoki Osawa
    • Journal Title

      Heliyon

      Volume: 4 Issue: 6 Pages: e00639-e00639

    • DOI

      10.1016/j.heliyon.2018.e00639

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 心筋リポフスチン沈着の法医診断的活用2019

    • Author(s)
      垣本 由布, 長尾 涼子, 落合 恵理子, 瀬戸 良久、大澤 資樹
    • Organizer
      第103次日本法医学会学術全国集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 加齢に伴う心筋リポフスチン沈着とオートファジー機能2019

    • Author(s)
      垣本由布、岡田千沙、河邉昇、長尾涼子、大澤資樹
    • Organizer
      第108回日本病理学総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Overexpression of MiR-221 as an Indicator of Sudden Death with Cardiac Hypertrophy2018

    • Author(s)
      Kakimoto Y, Kakiuchi Y, Ochiai E, Osawa M
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生理的心肥大および病的心肥大におけるマクロRNAの発現プロファイリング2018

    • Author(s)
      垣本由布、田中政之、林英樹、横山圭子、大澤資樹
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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

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