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Regulation of Endothelial Function by ROCK2

Research Project

Project/Area Number 23790882
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

KAWANAMI DAIJI  東京慈恵会医科大学, 医学部, 講師 (50568889)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords動脈硬化 / 血管内皮 / Rho-kinase / Rho / ROCK2 / ROCK / 小胞体ストレス
Research Abstract

The process of atherosclerosis is affected by interactions among numerous biological pathways. Accumulating evidence shows that small GTP-binding protein Rho and its effector Rho-kinase (ROCK) play an important role in the development of atherosclerosis. ROCK has two isoforms, ROCK1 and ROCK2. However, it is unclear how ROCK2 regulates endothelial function. To this end, we first examined the effect of ROCK inhibitors on endothelial function. We found that ROCK inhibitors such as Y-27632 and fasudil attenuates endothelial inflammation markers including MCP-1. Furthermore, knockdown of ROCK2 reduced MCP-1 expression levels in endothelial cells. Finally, we isolated peritoneal macrophages from ROCK2-deficient and wild-type mice. LPS induced MCP-1 expression in the cells derived from wild-type. Interestingly, induction of MCP-1 was inhibited in ROCK2-deficient cells. These finding indicate that ROCK2 plays an important role in the development of atherosclerosis.

Report

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

    (19 results)

All 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Fasudil inhibits ER stress-induced VCAM-1 expression by modulating unfolded protein response in endothelial cells2013

    • Author(s)
      Kawanami D, Matoba K, Okada R, Tsukamoto M, Kinoshita J, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 435 Pages: 171-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] The Rho-kinase inhibitor fasudil restores normal motor nerve conduction velocity in diabetic rats by assuring the proper localization of adhesion-related molecules in myelinating Schwann cells2013

    • Author(s)
      Kanazawa Y, Takahashi-Fujigasaki J, Ishizawa S, Takabayashi N, Ishibashi K, Matoba K, Kawanami D, Yokota T, Tajima N, Utsunomiya K
    • Journal Title

      Exp Neurol

      Volume: 247 Pages: 438-46

    • Related Report
      2013 Final Research Report
  • [Journal Article] Rho-kinase inhibition prevents the progression of diabetic nephropathy by downregulating hypoxia-inducible factor 1α2013

    • Author(s)
      Matoba K, Kawanami D, Okada R, Tsukamoto M, Kinoshita J, Ito T, Ishizawa S, Kanazawa Y, Yokota T, Murai N, Matsufuji S, Takahashi-Fujigasaki J, Utsunomiya K
    • Journal Title

      Kidney Int

      Volume: 84 Pages: 545-54

    • Related Report
      2013 Final Research Report
  • [Journal Article] Fasudil inhibits ER stress-induced VCAM-1 expression by modulating unfolded protein response in endothelial cells.2013

    • Author(s)
      Daiji Kawanami
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 435 Issue: 2 Pages: 171-175

    • DOI

      10.1016/j.bbrc.2013.04.091

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rho-kinase inhibition prevents the progression of diabetic nephropathy by downregulating hypoxia-inducible factor 1a2013

    • Author(s)
      Matoba K, Kawanami D, Okada R, Tsukamoto M, Kinoshita J, Ito T, Ishizawa S, Kanazawa Y, Yokota T, Murai N, Matsufuji S, Takahashi-Fujigasaki J, Utsunomiya K
    • Journal Title

      Kidney International

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fasudil Inhibits ER Stress-induced VCAM-1 Expression by Modulating Unfolded Protein Response in Endothelial Cells2013

    • Author(s)
      Kawanami D, Matoba K, Okada R, Tsukamoto M, Kinoshita J, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation2012

    • Author(s)
      Haldar SM, Jeyaraj D, Anand P, Zhu H, Lu Y, Prosdocimo DA, Eapen B, Kawanami D, Okutsu M, Brotto L, Fujioka H, Kerner J, Rosca MG, McGuinness OP, Snow RJ, Russell AP, Gerber AN, Bai X, Yan Z, Nosek TM, Brotto M, Hoppel CL, Jain MK
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Pages: 6739-44

    • Related Report
      2013 Final Research Report
  • [Journal Article] Thrombin induces MCP-1 expression through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway activation in vascular endothelial cells2011

    • Author(s)
      Kawanami D, Matoba K, Kanazawa Y, Ishizawa S, Yokota T, Utsunomiya K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 411 Pages: 798-803

    • Related Report
      2013 Final Research Report
  • [Journal Article] Thrombin induces MCP-1 expression through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway activation in vascular endothelial cells2011

    • Author(s)
      Kawanami D, Matoba K, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 411 Pages: 798-803

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Rho-kinaseの活性化はER stressに伴う血管内皮機能障害に関与する2013

    • Author(s)
      川浪大治
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Rho-kinase inhibition attenuates endothelial inflammation by modulating ER stress signaling2013

    • Author(s)
      Daiji Kawanami
    • Organizer
      73rd American Diabetes Association
    • Place of Presentation
      シカゴ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Rho-kinase mediates ER stress-induced endothelial dysfunction2012

    • Author(s)
      Kawanami D, Matoba K, Okada R, Tsukamoto M, Kinoshita J, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Organizer
      72nd American Diabetes Association Scientific Sessions
    • Place of Presentation
      アメリカ合衆国フィラデルフィア
    • Related Report
      2012 Research-status Report
  • [Presentation] Rho-kinaseの活性化がER stressによる血管内皮機能障害を促進する2012

    • Author(s)
      川浪大治、的場圭一郎、岡田梨奈、塚本雅美、木下淳、伊藤朝子、石澤将、金澤康、横田太持、宇都宮一典
    • Organizer
      55回 日本糖尿病学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Rho/Rho-kinase mediates thrombin-induced MCP-1 induction in vascular endothelial cells2011

    • Author(s)
      Kawanami D, Matoba K, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Organizer
      71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ
    • Related Report
      2011 Research-status Report
  • [Presentation] mDia1はlysophosphatidic acidによる血管内皮機能障害を制御する

    • Author(s)
      川浪大治
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Related Report
      2013 Final Research Report
  • [Presentation] Rho-kinase inhibition attenuates endothelial inflammation by modulating ER stress signaling

    • Author(s)
      Daiji Kawanami
    • Organizer
      73^<rd> American Diabetes Association Scientific Sessions
    • Related Report
      2013 Final Research Report
  • [Presentation] Rho-kinaseの活性化はERストレスに伴う血管内皮機能障害に関与する

    • Author(s)
      川浪大治
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Related Report
      2013 Final Research Report
  • [Presentation] Rho-kinase is involved in diabetic nephropathy by modulating HIF-1alpha-dependent signaling pathway

    • Author(s)
      Daiji Kawanami
    • Organizer
      第9回国際糖尿病連合西太平洋地区会議/第4回アジア糖尿病学会
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.diabendo.jp/

    • Related Report
      2011 Research-status Report

URL: 

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

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