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Analysis of the function of endothelial ROCK1 in pulmonary hypertension

Research Project

Project/Area Number 18590812
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

RIKITAKE Yoshiyuki  Kobe University, Graduate Schcol of Medicine, Assistant Professor (50419488)

Co-Investigator(Kenkyū-buntansha) 横山 光宏  神戸大学, 医学系研究科, 教授 (40135794)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,910,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsvascular endothelial cell / ROCKI / signal transduction
Research Abstract

I investigated to analyze the roles of ROCK1 in regulation mechanism of vascular diseases by ROCK1 and obtained the following results.
1. The role of ROCK1 in vascular remodeling was analyzed using mouse common carotid ligation model. Intimal thickening and stenosis in carotid arteries in ROCK1+/- mice were reduced as compared to those in wild-type mice.
2. Vascular inflammation and DNA synthesis of vascular wall cells after carotid ligation in ROCK1+/- mice were reduced as compared to those in wild-type mice.
3. Similarly to ROCK1+/- mice, reduced vascular remodeling was observed in wild-type mice received bone marrow transplantation of ROCK1+/- mice.
4. Vascular endothelial cells primary cultured from ROCK1+/- mice showed reduced ROCK activity and inhibition of adhesion molecule expression as compared to those from wild-type mice.
5. Vascular smooth muscle cells obtained from ROCK1+/- mice showed reduced ROCK activity and inhibition of cell migration as compared to those from wild-type mice.
6. Inhibition of ROCK reduced maturation of focal complex to focal adhesion and cell movement.
7. Inhibition of ROCK stimulated BH4 synthesis and thereby increased nitric oxide production in endothelial cells.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (6 results)

All 2008 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] Roles of Necl-5/poliovirus receptor and ROCK in the regulation of transformation of integrin αvβ_3-based focal complexes into focal adhesions2008

    • Author(s)
      Nagamatsu Y., et. al.
    • Journal Title

      Journal of Biological Chemistry (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sequential activation of Rap 1 and Racl small G proteins by PDGF locally at leading edges of NIH3T3 cells2008

    • Author(s)
      Takahashi M., et. al.
    • Journal Title

      Genes to Cells (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Roles of Nec1-5/poliovirus receptor and Rho-associated kinase(ROCK)in the regulation of transformation of integrin αVβ3-based focal complexes into focal adhesions

    • Author(s)
      Yuichi, Nagamatsu, Yoshiyuki, Rikitake, Motonori, Takahashi, Yuko, Deki, Wataru, Ikeda, Kenichi, Hirata, Yoshimi, Takai
    • Journal Title

      Journal of Biological Chemistry (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sequential activation of Rap 1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells

    • Author(s)
      Motonori, Takahashi, Yoshiyuki, Rikitake, Yuichi, Nagamatsu, Tetsuya, Hara, Wataru, Ikeda, Ken-ichi, Hirata, Yoshimi, Takai
    • Journal Title

      Genes to Cells (in press)

    • NAID

      120001384732

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulation of in vitro angiogenesis by Rap 1-afadin pathway2008

    • Author(s)
      Takahashi M., et. al.
    • Organizer
      第72回日本循環器学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2008-03-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulation of in vitro angiogenesis by Rap Paladin pathway2008

    • Author(s)
      Motonori, Takahashi, Yoshiyuki, Rikitake, Yoshimi, Takai, Ken-ichi, Hirata
    • Organizer
      The 72nd Annual Scientific Meeting of The Japanese Circulation Society
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2008-03-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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