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Application of a novel nucleic acid agent for chymase-specific inhibition

Research Project

Project/Area Number 18K06709
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionOsaka Medical College

Principal Investigator

TAKAI Shinji  大阪医科大学, 医学研究科, 教授 (80288703)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsキマーゼ / 核酸製剤 / 阻害薬 / 心筋梗塞 / 心不全 / ハムスター / 心機能 / 線維化 / 生存率 / 炎症
Outline of Final Research Achievements

We investigated the effect of a novel nucleic acid compound that specifically inhibits chymase on heart failure after myocardial infarction. Cardiac chymase activity was significantly increased after myocardial infarction, but it was significantly suppressed by the nucleic acid compound. Cardiac mRNA levels of TGF-β and collagen increased after myocardial infarction were significantly reduced by the nucleic acid compound. Cardiac function reduced after myocardial infarction was also significantly improved by the nucleic acid preparation, and the mortality rate was significantly reduced. The nucleic acid compound with specific chymase inhibition was useful in the prevention of heart failure after myocardial infarction.

Academic Significance and Societal Importance of the Research Achievements

心筋梗塞を起こした患者は、心筋梗塞後に心不全に陥っていくが、特異的にキマーゼを阻害する核酸製剤が心筋梗塞直後からの投与でその進行を予防することを示した。この核酸製剤のキマーゼに対する特異性は既存の低分子キマーゼ阻害薬よりも極めて高く、低濃度でも有用であった。核酸製剤は、心筋梗塞後の心不全予防において新しい治療戦略になる可能性を示した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2019 2018

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

  • [Journal Article] Chymase inhibition retards albuminuria in type 2 diabetes2019

    • Author(s)
      Bivona Benjamin J.、Takai Shinji、Seth Dale M.、Satou Ryousuke、Harrison‐Bernard Lisa M.
    • Journal Title

      Physiological Reports

      Volume: 7 Issue: 24

    • DOI

      10.14814/phy2.14302

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Chymase Inhibitory RNA Aptamer Improves Cardiac Function and Survival after Myocardial Infarction2019

    • Author(s)
      Jin Denan、Takai Shinji、Nonaka Yosuke、Yamazaki Satoko、Fujiwara Masatoshi、Nakamura Yoshikazu
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 14 Pages: 41-51

    • DOI

      10.1016/j.omtn.2018.11.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] An antichymase RNA aptamer improved cardiac function in experimental heart failure.2018

    • Author(s)
      Jin D, Takai S, Nonaka Y, Yamazaki S, Fujiwara M, Nakamura Y.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規RNAアプタマーによるキマーゼ阻害と心筋梗塞後の心機能および生存率の改善効果2018

    • Author(s)
      金徳男、髙井真司、野中洋介、山﨑聡子、藤原将寿、中村義一
    • Organizer
      第23回日本病態プロテアーゼ学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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