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Translational research of lymphangiogenesis for cardiovascular diseases

Research Project

Project/Area Number 17H06745
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Cardiovascular medicine
Research InstitutionNagoya University

Principal Investigator

Shimizu Yuuki  名古屋大学, 医学部附属病院, 助教 (90801887)

Research Collaborator MUROHARA toyoaki  
Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsリンパ管新生 / 2次性リンパ浮腫 / 硫化水素 / Lymphangiogenesis / Secondary lymphedema / Hydrogen sulfide / Akt / eNOS / リンパ浮腫 / DATS
Outline of Final Research Achievements

Lymphedema is one of the serious clinical problems which can occur after surgical resection of malignant tumors such as breast cancer or intra-pelvic cancers. However, no effective treatment options exist at present. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil and able to release H2S through interactions with biological thiols, including glutathione. So, DATS can act as a H2S donor. Previously we reported that DATS can promote angiogenesis in hind limb ischemia. However, it is currently unknown whether H2S can augment lymphangiogenesis and improve lymphedema.
In a present project, our data documented that DATS functions as a novel regulator of lymphatic-vascular responses to lymphedema and importantly, therapeutic approaches aimed at augmenting exogenous H2S using H2S-releasing agents could be potentially useful for treating secondary lymphedema.

Academic Significance and Societal Importance of the Research Achievements

心血管病に対してリンパ管新生を調節することを標的とした、いわゆる「治療的リンパ管新生」研究を進めていく事により、これまで有効な治療法が存在しなかった難治性心血管病に対する別の角度からの病態の解明と理解(学術的意義)、および新たなアプローチによる新規治療法の開発につながる(社会的意義)。
本研究により、「硫化水素を用いたリンパ浮腫に対する治療的リンパ管新生」を小動物(哺乳類)において検証し、トランスレーショナルリサーチとしての成果を得ることができた。今後は本研究を発展させ、大型動物での検証、臨床導入への応用などが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (6 results)

All 2019 2018 Other

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

  • [Int'l Joint Research] エモリー大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury.2018

    • Author(s)
      Shimizu Y, Polavarapu R, Eskla KL, Pantner Y, Nicholson CK, Ishii M, Brunnhoelzl D, Mauria R, Husain A, Naqvi N, Murohara T, Calvert JW.
    • Journal Title

      J Am Heart Assoc.

      Volume: 7 Issue: 19

    • DOI

      10.1161/jaha.118.009565

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK.2018

    • Author(s)
      Shimizu Y, Polavarapu R, Eskla KL, Nicholson CK, Koczor CA, Wang R, Lewis W, Shiva S, Lefer DJ, Calvert JW
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 116 Pages: 29-40

    • DOI

      10.1016/j.yjmcc.2018.01.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] シンポジウム12 再生医療の最前線 「脂肪組織由来間葉系前駆細胞を用いた血管再生療法」2019

    • Author(s)
      清水 優樹
    • Organizer
      第17回日本フットケア学会年次学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Lymphangiogenesis Contributes to the Ischemia Induced Angiogenesis via Clearance of Inflammation in Hind Limb Ischemia2019

    • Author(s)
      浦 鐘月 清水 優樹
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] 医学のあゆみ2019

    • Author(s)
      清水優樹、室原豊明
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Annual Research Report

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Published: 2017-08-25   Modified: 2022-05-23  

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