• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

キマーゼの心血管組識線維化における病態生理学的役割

Research Project

Project/Area Number 16659068
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionOsaka Medical College

Principal Investigator

高井 真司  大阪医科大学, 医学部, 助教授 (80288703)

Co-Investigator(Kenkyū-buntansha) 金 徳男  大阪医科大学, 医学部, 講師 (90319533)
村松 理子  大阪医科大学, 医学部, 助手 (30330096)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsキマーゼ / Transforming growth factor-β / アンジオテンシンII / 組織繊維化 / 肥満細胞 / 阻害薬 / 心臓 / 血管 / 組織線維化
Research Abstract

昨年度に検討したイヌ動静脈シャント後の血管肥厚におけるキマーゼのTransforming Growth Factor-β活性化を介した役割について、研究発表に記載したとおり論文化することができた(Jin et al.,J Am Soc Nephrol 2005;16:1024-1034)。本年度は、昨年度より行っていたラット心筋梗塞モデルを用いた研究の追加を行った。ラット心筋梗塞後2週の時点でキマーゼ活性およびコラーゲンI、コラーゲンIII、Transforming growth factor-βの発現増加が見られた。ラットキマーゼは、アンジオテンシンIIを産生しないことより、キマーゼは、Transforming growth factor-βの活性化を介して心筋梗塞後の心臓線維化に深く関与しているものと考えられる。この心臓線維化は、キマーゼ阻害薬を投与することにより、キマーゼ活性低下および、コラーゲンI、コラーゲンIII、Transforming growth factor-βの発現減少を伴っていた(研究発表:Kanemitsu et al., Hypertens Res.)。これらのデータは、キマーゼがアシジオテンシンIIを介さずともTransforming growth factor-βの活性化を介し心血管線維化を促進させることを示唆するものである。さらに、心筋梗塞を作製後1ヶ月の時点で、心筋線維化部位を手術的に摘出し、残存心筋を繋ぎ合わせ(ドール術モデル)、その後に見られる線維化に対し、キマーゼ阻害薬が有効であることも確認し(2005年、米国心臓学会にて報告)、現在、論文投稿中である。

Report

(2 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats2006

    • Author(s)
      Kanemitsu H
    • Journal Title

      Hypertension Research 29・1

      Pages: 57-64

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of chymase inhibition on the artheriovenous fistula stenosis in dog2005

    • Author(s)
      Jin D
    • Journal Title

      Journal of American Society of Nephrology 16・4

      Pages: 1024-1034

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats2005

    • Author(s)
      Kirimura K
    • Journal Title

      Hypertension Research 28・5

      Pages: 429-435

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mast cell chymase induces conjunctival epithelial cell apoptosis by a mechanism involving degradation of fibronectin2005

    • Author(s)
      Ebihara N
    • Journal Title

      Current Eye Research 30・6

      Pages: 429-435

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Eplerenone inhibits atherosclerosis in non-human primates2005

    • Author(s)
      Takai S
    • Journal Title

      Hypertension 46・5

      Pages: 1135-1139

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet2005

    • Author(s)
      Takai S
    • Journal Title

      Journal of Hypertension 23・10

      Pages: 1879-1886

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Therapeutic applications of chymase inhibitors in cardiovascular diseases and fibrosis2004

    • Author(s)
      Takai S
    • Journal Title

      European Journal of Pharmacology 501

      Pages: 501-508

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters2004

    • Author(s)
      Sakaguchi M
    • Journal Title

      European Journal of Pharmacology 493

      Pages: 173-176

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of a chymase inhibitor, Suc-Pro-PheP(OPh)_2, on growth of cultured canine Tenon's capsule fibroblasts and scarring in a canine conjunctival flap model2004

    • Author(s)
      Maruichi M
    • Journal Title

      Experimental Eye Research 79・1

      Pages: 111-118

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model2004

    • Author(s)
      Takai S
    • Journal Title

      Hypertension Research 27・7

      Pages: 517-522

    • NAID

      10013515786

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effect of chymase-dependent transforming growth factor beta on peritoneal adhesion formation in a rat model2004

    • Author(s)
      Okamoto Y
    • Journal Title

      Surgery Today 34・10

      Pages: 865-867

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chymase as a novel target for prevention of vascular diseases2004

    • Author(s)
      Takai S
    • Journal Title

      Trends in Pharmacological Sciences 25・10

      Pages: 518-522

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi