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Pathophysiological role of chymase in complications of metabolic syndrome

Research Project

Project/Area Number 20590265
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOsaka Medical College

Principal Investigator

TAKAI Shinji  Osaka Medical College, 医学部, 准教授 (80288703)

Co-Investigator(Kenkyū-buntansha) JIN Denan  大阪医科大学, 医学部, 講師 (90319533)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsキマーゼ / メタボリックシンドローム / 糖尿病 / 高脂血症 / 臓器障害 / 脂肪肝 / 線維化 / 大動脈瘤 / 高血圧 / 動脈硬化 / 肝線維化 / 阻害薬 / 内皮機能障害 / 臓器線維化
Research Abstract

Chymase converts precursors of angiotensin (Ang) II, Transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 to their active forms. In a diabetic animal model, chymase induced pancreatic disorganization by augmentation of chymase-forming Ang II. In an animal model with abdominal aneurysmal aorta (AAA), the inhibition of MMP-9 activation by chymase inhibitor resulted in attenuation of the AAA progression. Steatosis and fiblosis in liver were strongly prevented by chymase inhibition in an animal model with nonalcoholic steatohepatitis. These results demonstrated that chymase plays a crucial role in complications of metabolic syndrome.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (37 results)

All 2011 2010 2009 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (14 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats2011

    • Author(s)
      Shinji Takai
    • Journal Title

      Hypertension Research

      Volume: 34 Pages: 245-252

    • NAID

      10031163160

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targets of chymase inhibitors2011

    • Author(s)
      Shinji Takai
    • Journal Title

      Expert Opinion on Therapeutic Targets

      Volume: 15 Pages: 519-527

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase as an important target for preventing complications of metabolic syndrome.2010

    • Author(s)
      Takai S, Jin D, Miyazaki M
    • Journal Title

      Curr Med Chem 17

      Pages: 3223-3229

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chymase as an important target for preventing complications of metabolic syndrome2010

    • Author(s)
      Shinji Takai
    • Journal Title

      Current Medicinal Chemistry

      Volume: 17 Pages: 3223-3229

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New approaches to blockade of the renin-angiotensin-aldosterone system : chymase as an important target to prevent organ damage2010

    • Author(s)
      Shinji Takai
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 113 Pages: 301-309

    • NAID

      10027745795

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibition attenuates tetrachloride-induced liver fibrosis in hamsters2010

    • Author(s)
      Koji Komeda
    • Journal Title

      Hepatology Research

      Volume: 40 Pages: 832-840

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibitor prevents the nonalcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet2010

    • Author(s)
      Keitaro Tashiro
    • Journal Title

      Hepatology Research

      Volume: 40 Pages: 514-523

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy2010

    • Author(s)
      Daisuke Yamamoto
    • Journal Title

      Clinica Chimica Acta

      Volume: 411 Pages: 762-764

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy with irbesartan and efonidipine for attenuation of proteinuria in Dahl salt-sensitive rats2010

    • Author(s)
      Shinji Takai
    • Journal Title

      Hypertension Research

      Volume: 33 Pages: 953-959

    • NAID

      10026711303

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of acute myocardial ischemia reperfusion on the tissue and blood-born renin-angiotensm system2010

    • Author(s)
      Shizu Oyamada
    • Journal Title

      Basic Research in Cardiology

      Volume: 105 Pages: 513-522

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of chymase-dependent matrix metalloproteinase-9 activation on indomethacin-induced small intestinal damages in rats2010

    • Author(s)
      Kazuki Kakimoto
    • Journal Title

      J.Pharmacol.Exp.Ther. 332

      Pages: 684-689

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of chymase inhibitor on angiotensin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice.2009

    • Author(s)
      Inoue N, Jin D, Takai S, et al
    • Journal Title

      Atherosclerosis 204(2)

      Pages: 359-364

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chymase-dependent conversion of exogenously administered big endothelin-1 in the mouse in vivo.2009

    • Author(s)
      Simard E, Jin D, Takai S, et al
    • Journal Title

      J Pharmacol Exp Ther 328(2)

      Pages: 540-548

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term angiotensin II blockade may improve not only hyperglycemia but also age-associated cardiac fibrosis.2009

    • Author(s)
      Jin D, Takai S, et al
    • Journal Title

      J Pharmacol Sci 109(2)

      Pages: 275-284

    • NAID

      10025734617

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice.2009

    • Author(s)
      Matsumoto C, Jin D, Takai S, et al
    • Journal Title

      Hypertension 54(1)

      Pages: 164-171

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibition provides pancreatic islet protection in hamsters with streptozotocin-induced diabetes2009

    • Author(s)
      Shinji Takai
    • Journal Title

      J.Pharmacol.Sci. 110

      Pages: 459-465

    • NAID

      10025738252

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of chymase inhibitor on angiotensin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice2009

    • Author(s)
      Nao Inoue
    • Journal Title

      Atherosclerosis 204

      Pages: 359-364

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice2009

    • Author(s)
      Chika Matsumoto
    • Journal Title

      Hypertension 54

      Pages: 164-171

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-atherosclerotic effects of dihomo-γ-linolenic acid in apoE-deficient mice2009

    • Author(s)
      Shinji Takai
    • Journal Title

      J.Atheroscler.Thromb. 16

      Pages: 480-488

    • NAID

      10025766711

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of vascular angiotensin II-forming enzymes in the progression of aortic abdominal aneurysms in angiotensin II-infused apoE-deficient mice2009

    • Author(s)
      Nao Inoue
    • Journal Title

      J.Atheroscler.Thromb. 16

      Pages: 359-364

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term angiotensin II blockade may improve not only hyperglycemi a but also age-associated cardiac fibrosis2009

    • Author(s)
      Jin Denan (金徳男)
    • Journal Title

      J. Pharmacol. Sci. 109

      Pages: 275-284

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chymase as a useful target to prevent abdominal aortic aneurysm.2011

    • Author(s)
      Takai S, Jin D, Miyazaki M
    • Organizer
      Keystone Symposia
    • Place of Presentation
      リノ、米国
    • Year and Date
      2011-01-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Chymase as a useful target to prevent abdominal aortic aneurysm2011

    • Author(s)
      Shinji Takai
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Granlibakken Ressort (California, USA)
    • Year and Date
      2011-01-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] キマーゼ阻害薬による腹部大動脈瘤予防の可能性2010

    • Author(s)
      高井真司
    • Organizer
      第38回薬物活性シンポジウム
    • Place of Presentation
      札幌市教育文化会館(北海道)
    • Year and Date
      2010-11-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] キマーゼ阻害薬による腹部大動脈瘤進展予防の可能性(シンポジウム)2010

    • Author(s)
      高井真司、金徳男、宮崎瑞夫
    • Organizer
      第38回薬物活性シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2010-11-11
    • Related Report
      2010 Final Research Report
  • [Presentation] カンデサルタンとアムロジピンの併用投与による血管保護相乗効果の機序2010

    • Author(s)
      高井真司
    • Organizer
      日本高血圧学会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2010-10-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Combination therapy with angiotensin receptor blocker and T- and L-type calcium channel blocker for attenuation of proteinuria in Dahlsalt-sensitive rats2010

    • Author(s)
      Shinji Takai
    • Organizer
      23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Vancouver Convention Centre (Vancouver, Canada)
    • Year and Date
      2010-09-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] Combination therapy with angiotensin receptor blocker and T- and L-type calcium channel blocker for attenuation of proteinuria in Dahl-salt sentitive rats.2010

    • Author(s)
      高井真司, 金徳男, et al
    • Organizer
      23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-26
    • Related Report
      2010 Final Research Report
  • [Presentation] キマーゼ阻害薬による腹部大動脈瘤の進展抑制2010

    • Author(s)
      高井真司
    • Organizer
      生体機能と創薬シンポジウム2010京都
    • Place of Presentation
      ホテルグランビア京都(京都)(招待講演)
    • Year and Date
      2010-09-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] キマーゼ阻害薬のターゲット疾患について(シンポジウム)2010

    • Author(s)
      高井真司、金徳男、宮崎瑞夫
    • Organizer
      第15回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2010-08-20
    • Related Report
      2010 Final Research Report
  • [Presentation] キマーゼ阻害薬のターゲット疾患について2010

    • Author(s)
      高井真司
    • Organizer
      第15回日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)(招待講演)
    • Year and Date
      2010-08-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 特異的キマーゼ阻害薬TY-51469によるハムスター非アルコール性脂肪性肝炎の阻害効果2010

    • Author(s)
      山本裕美
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2010-03-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝炎(NASH)ハムスターモデルにおけるキマーゼ阻害薬の効果2009

    • Author(s)
      田代圭太郎
    • Organizer
      第14回日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2009-08-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] キマーゼ阻害薬の開発と臓器保護効果(シンポジウム)2009

    • Author(s)
      高井真司、金徳男、宮崎瑞夫
    • Organizer
      日本薬理学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] キマーゼ阻害薬の開発と臓器保護効果2009

    • Author(s)
      高井真司
    • Organizer
      第82回日本薬理学会年会(シンポジウム)
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Annual Research Report
  • [Book] 日本臨床 高血圧(第4版) 上巻2009

    • Author(s)
      高井真司
    • Publisher
      日本臨床社
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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