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Significance of chymase inhibition to prevent the complication of metabolic syndrome

Research Project

Project/Area Number 23590313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionOsaka Medical College

Principal Investigator

TAKAI Shinji  大阪医科大学, 医学部, 准教授 (80288703)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsキマーゼ / メタボリックシンドローム / 合併症 / 阻害薬 / 高血圧 / NASH / 脳卒中 / 血管障害 / NASH / 肝臓線維化 / 炎症 / 血管機能障害 / 心機能障害 / 腎機能障害 / アンジオテンシンII / 心臓障害 / 腎臓障害 / 動脈硬化
Research Abstract

Effects of the chymase inhibitor were evaluated on animal models with the non-alcoholic steatohepatitis (NASH) and stroke-prone spontaneously hypertensive (SHR-SP) rats as complications of the metabolic syndrome. In a hamster NASH model, plasma levels of AST and ALT were improved by the chymase inhibitor and the improvement of lipid deposition and fibrosis was also observed. In SHR-SP rats, the chymase inhibitor showed to prevent the vascular endothelial dysfunction via the anti-oxidative effect and the prevention of inflammatory cell-infiltration into the endothelium without hypotensive effect. The chymase inhibitor also extended the survival term.
These results suggest that chymase inhibition become the useful strategy to prevent the complication of metabolic syndrome.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (7 results)

  • [Journal Article] Chymase inhibition improves vascular dysfunction and survival in stroke-prone spontaneously hypertensive rats2014

    • Author(s)
      Takai S, Jin D, Chen H, Li W, Yamamotoc H, Yamanishi K, Miyazaki M, Higashino H, Yamanishi H, Okamura H.
    • Journal Title

      Journal of Hypertension

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibitor ameliorates hepatic steatosis and fibrosis on established non-alcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet2013

    • Author(s)
      Masubuchi S, Takai S, Jin D, Tashiro K, Komeda K, Li ZL, Otsuki Y, Okamura H, Hayashi M, Uchiyama K
    • Journal Title

      Hepatol Res

      Volume: Vol.43、No.9 Pages: 970-978

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibitor ameliorates hepatic steatosis and fibrosis on established non-alcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet.2013

    • Author(s)
      Masubuchi S, Takai S, Jin D, Tashiro K, Komeda K, Li ZL, Otsuki Y, Okamura H, Hayashi M, Uchiyama K.
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 9 Pages: 970-978

    • DOI

      10.1111/hepr.12042

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibition attenuates lipopolysaccharide/ d-galactosamine-induced acute liver failure in hamsters2013

    • Author(s)
      Imai Y, Takai S, Jin D, Komeda K, Tashiro K, Li ZL, Otsuki Y, Okamura H, Hayashi M, Uchiyama K.
    • Journal Title

      Pharmacology

      Volume: 40 Issue: 1-2 Pages: 832-840

    • DOI

      10.1159/000357684

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase Inhibition Attenuates Monocrotaline-Induced Sinusoidal Obstruction Syndrome in Hamsters.2013

    • Author(s)
      Masubuchi S, Komeda K, Takai S, Jin D, Tashiro K, Li ZL, Otsuki Y, Otsuki Y, Okamura H, Hayashi M, Uchiyama K.
    • Journal Title

      Curr Med Chem

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pivotal role of mouse mast cell protease 4 in the conversion and pressor properties of big-endothelin-1.2013

    • Author(s)
      Houde M, Jamain MD, Labonte J, Desbiens L, Pejler G, Gurish M, Takai S, D'Orleans-Juste P.
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cisplati-induced acute renal failure in mice is mediated by chymase-activated angiotensin-aldosterone system and interleukin-182012

    • Author(s)
      Shin Okui
    • Journal Title

      European Journal of Pharmacology

      Volume: 685 Issue: 1-3 Pages: 149-155

    • DOI

      10.1016/j.ejphar.2012.04.027

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibition improves vascular dysfunction and survival in stroke-prone spontaneously hypertensive rats

    • Author(s)
      Takai S, Jin D, Chen H, Li W, Yamamoto H, Yamanishi K, MiyazakiM, Higashino H, Yamanishi H, Okamura H
    • Journal Title

      J Hypetens

      Volume: (In press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 脳卒中易発性高血圧自然発症ラットの血管障害に対するキマーゼ阻害薬の効果2013

    • Author(s)
      髙井真司, 金徳男, 陳紅, 李文, 山本英幸, 山西恭輔, 宮崎瑞夫, 山西博道, 岡村春樹
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 脳卒中易発性高血圧自然発症ラットの血管障害におけるキマーゼの役割2013

    • Author(s)
      髙井真司, 金徳男, 陳紅, 李文, 山本英幸, 山西恭輔, 宮崎瑞夫, 山西博道, 岡村春樹
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2013-10-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 脳卒中易発性高血圧自然発症ラットの血管障害および生存期間に対するキマーゼ阻害薬の効果2013

    • Author(s)
      高井真司、金徳男、陳紅、李文、山本英幸、山西恭輔、宮崎瑞夫、岡村春樹
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脳卒中易発性高血圧自然発症ラットの血管障害におけるキマーゼの役割2013

    • Author(s)
      高井真司、金徳男、陳紅、李文、山本英幸、山西恭輔、宮崎瑞夫、岡村春樹
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] A chymase inhibitor, ty-51469, ameliorates already formed hepatic steatosis and fibrosis in a hamster nonalcoholic steatohepatitis (nash) model2012

    • Author(s)
      Masubuchi S, Takai S, Jin D, Tashiro K, Komeda K, Hayashi M, Uchiyama K
    • Organizer
      63th Annual meeting of American Association for the Study of Liver Diseases
    • Place of Presentation
      ボストン(米国)
    • Year and Date
      2012-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 1. A chymase inhibitor, ty-51469, ameliorates already formed hepatic steatosis and fibrosis in a hamster nonalcoholic steatohepatitis (nash) model.2012

    • Author(s)
      Masubuchi S, Takai S, Jin D, Tashiro K, Komeda K, Hayashi M, Uchiyama K.
    • Organizer
      63th Annual meeting of American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] ハムスターNASHモデルに対するキマーゼ阻害薬の治療効果の検討2012

    • Author(s)
      鱒渕真介、髙井真司、金徳男、田代圭太郎、米田浩二、林道廣、内山和久
    • Organizer
      第17回日本病態プロテアーゼ学会
    • Place of Presentation
      浜松、静岡県
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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