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Role of Rho/Rho-kinase-mediated pathway in the pathogenesls of atherosclerosis

Research Project

Project/Area Number 13307024
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyushu University

Principal Investigator

SHIMOKAWA Hiroaki (2003)  Kyushu University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Associate Professor, 大学院・医学研究院, 助教授 (00235681)

竹下 彰 (2001-2002)  九州大学, 大学院・医学研究院, 教授 (30038814)

Co-Investigator(Kenkyū-buntansha) ITO masaaki  Mie University, Dept.of Int.Med., Assistant Professor, 医学部, 講師 (00223181)
KAIBUCHI Kozo  Nagoya University, Dept.of Cell Pharmacology, Professor, 大学院・医学研究科, 教授 (00169377)
SUEISHI Katsuo  Kyushu University, Dept.of Pathophysiol.Exp.Pathology, Professor, 大学院・医学研究院, 教授 (70108710)
ICHIKI Toshihiro  Kyushu University, Dept.of Cardiovasc Med., Assistant Professor, 助手 (80311843)
KOIKE George  Kyushu University, Dept.of Cardiovasc Med., Assistant Professor, 助手 (90325522)
下川 宏明  九州大学, 大学院・医学研究院, 助教授 (00235681)
平川 洋次  九州大学, 医学部附属病院, 助手 (90332840)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥54,990,000 (Direct Cost: ¥42,300,000、Indirect Cost: ¥12,690,000)
Fiscal Year 2003: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2002: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2001: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
KeywordsRho-kinase / Vasospastic angina / Atherosclerosis / Cardiac hypertrophy / Restenosis / Myocardial infarction / Heart failure / Pulmonary hypertension / Rho-kinase / Rho / 炎症 / 狭心症 / シグナル伝達 / 冠動脈攣縮 / 高血圧
Research Abstract

(1)We have demonstrated that Rho/Rho-kinase-mediated pathway plays an important role in the pathogenesis of hypertension.
(2)We have demonstrated that Rho-kinase-mediated pathway is substantially involved in the pathogenesis of angiotensin II-induced cardiovascular hypertrophy in rats.
(3)We have demonstrated that Rho-kinase is located downstream of PKC in the signal transduction of vascular smooth muscle for coronary spasm in a porcine model.
(4)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of in-stent restenosis in porcine coronary arteries.
(5)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of LV remodeling after myocardial infarction in mice through inhibition of the expression of inflammatory cytokines.
(6)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of monocrotaline-induced pulmonary hypertension in rats.
(7)We have demonstrated that Rho-kinase is substantially mediated in the pathogenesis of microvascular angina.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Higashi M, Shimokawa H, et al.: "Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo."Circulation Research. 93. 767-775 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kandabashi T, Shimokawa H, et al.: "Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm."Arteriosclerosis, Thrombosis, and Vascular Biology. 23. 2209-2214 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto Y, ---, Shimokawa H.: "Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries -Involvement of multiple mechanisms-"Arteriosclerosis, Thrombosis, and Vascular Biology. 24. 181-186 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori T, Shimokawa H, et al.: "Long-term treatment with a specific Rho-kinase inhibitor suppresses cardiac allograft vasculopathy in mice."Circulation Research. 94. 46-52 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe K, Shimokawa H, et al.: "Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats."Circulation Research. 94. 385-393 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, Shimokawa H, et al.: "Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with angina and normal coronary angiograms."Journal of American College of Cardiology. 41. 15-19 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higashi M, Shimokawa H, et al.: "Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo."Circulation Research. 93. 767-775 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kandabashi T, Shimokawa H, et al.: "Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm."Arteriosclerosis, Thrombosis and Vascular Biology. 23. 2209-2214 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto Y, ---, Shimokawa H.: "Long-term inhibition of Rho-kinase suppresses Neointimal formation after stent implantation In porcine coronary arteries -Involvement of Multiple mechanisms-"Arteriosclerosis, Thrombosis and Vascular Biology. 24. 181-186 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori T, Shimokawa H, et al.: "Long-term treatment with a specific Rho-kinase inhibitor suppresses cardiac allograft vasculopathy in mice."Circulation Research. 94. 46-52 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe K, Shimokawa H, et al.: "Long-term treatment with a Rho-kinase Inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats."Circulation Research. 94. 385-393 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, Shimokawa H, et al.: "ho-kinase inhibition with intracoronary fasudil Prevents myocardial ischemia in patients with Angina with normal coronary arteries."Journal of American College of Cardiology. 41. 15-19 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higashi M, Shimolawa H, et al.: "Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo"Circulation Research. 93. 767-775 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kandabashi T, Shimokawa H, et al.: "Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm"Arteriosclerosis, Thrombosis, and Vascular Biology. 23. 2209-2214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsumoto Y, Shimokawa H: "Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries -Involvement of multiple mechanisms-"Arteriosclerosis, Thrombosis, and Vascular Biology. 24. 181-186 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori T, Shimokawa H, et al.: "Long-term treatment with a specific Rho-kinase inhibitor suppresses cardiac allograft vasculopathy in mice"Circulation Research. 94. 46-52 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe K, Shimokawa H, et al.: "Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats"Circulation Research. 94. 385-393 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mohri M, Shimokawa H, et al.: "Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with angina and normal coronary angiograms"Journal of American College of Cardiology. 41. 15-19 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masumoto A, Mohri M, Shimokawa H, et al.: "Suppression of coronary artery spasm by a Rho-kinase inhibitor fasudil in patients with vasospastic angina"Circulation. 105. 1545-1547 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kandabashi T, Shimokawa H, et al.: "Involvement of Rho-kinase in agonists-induced contractions of arteriosclerotic human arteries"Arterioscler Throm Vasc Biol.. 22. 243-248 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimokawa H, et al.: "Antianginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina : a multicenter study"J Cardiovasc Pharmacol.. 39. 319-327 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takemoto M, et al.: "Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase"Circulation. 106. 57-62 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimokawa H: "Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases"Journal of Cardiovascular Pharmacology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto A, Mohri M, Shimokawa H, et al.: "Suppression of coronary artery spasm by a Rho-kinase inhibitor in patients with vasospastic angina"Circulation. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kandabshi T, Shimokawa H, Mukai Y, et al.: "Involvement of Rho-kinase in agonists-induced contractions of arteriosclerotic human arteries"Arteriosclerosis Thrombosis Vascular Biology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto A, Hirooka Y, Shimokawa H, et al.: "Possible involvement of Rho-kinase in the pathogenesis of hypertension in hiumans"Hypertension. 38. 1307-1310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimokawa H, Morishige K, Miyata K, et al.: "Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo"Cardiovascular Research. 51. 169-177 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morishige K, Shimokawa H, Eto Y, et al.: "Adenovirus-mediated transfer of dominant-negative Rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo"Arteriosclerosis Thrombosis Vascular Biology. 21. 548-554 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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