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Roles of prostanoids in cardiovascular system revealed from studies using knockout mice

Research Project

Project/Area Number 14370049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionAsahikawa Medical College

Principal Investigator

USHIKUBI Fumitaka  Asahikawa Medical College, Pharmacology, Professor, 医学部, 教授 (50243035)

Co-Investigator(Kenkyū-buntansha) HARA Akiyoshi  Asahikawa Medical College, Pharmacology, Associate Professor, 医学部, 助教授 (90164988)
YUHKI Koh-ichi  Asahikawa Medical College, Pharmacology, Assistant Professor, 医学部, 助手 (80302420)
藤野 貴行  旭川医科大学, 医学部, 助手 (70322914)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywordsprostanoid / prostaglandin / thromboxane / 心臓 / 血管 / 虚血・再潅流
Research Abstract

The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attmpted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for pressure overload-induced cardiac hypertrophy and renovascular hypertention, and in vitro systems such as for cultures of cardiomyocytes from fetal or adult mice and culture of juxtagromerullar cells. We next examined the roles of the prostanoids using the established methods and knockout mice. Prostaglandin (PG) I_2 was found to be a potent inhibitor of cardiac hypertrophy consisting of cardiomyocyte hypertrophy and cardiac fibrosis via its receptor IP. PGI_2 playd an important pathophysiological role in the development of renovascular hypertension. This role was attained by the stimulation of the renin-angiotensine-aldosterone system by PGI_2. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles of the prostanoids in various pathological conditions such as cardiac ischemia-reperfusion injury, vascular remodeling and inflammatory tachycardia.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All 2004 Other

All Journal Article (5 results) Publications (3 results)

  • [Journal Article] Prostaglandin E_2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP_4.2004

    • Author(s)
      Xiao, C.-Y., Yuhki, K.et al.
    • Journal Title

      Circulation 109

      Pages: 2462-2468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I_2 receptor IP.2004

    • Author(s)
      Fujino, T., Nakagawa, N.et al.
    • Journal Title

      J.Clin.Invest. 114

      Pages: 805-812

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E_2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP_4.2004

    • Author(s)
      Xiao C-Y, et al.
    • Journal Title

      Circulation 109

      Pages: 2462-2468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I_2 receptor IP.2004

    • Author(s)
      Fujino T, et al.
    • Journal Title

      J.Clin.Invest. 114

      Pages: 805-812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E_2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP_42004

    • Author(s)
      Xiao, C.-Y., Yuhki, K.et al.
    • Journal Title

      Circulation 109

      Pages: 2462-2468

    • Related Report
      2004 Annual Research Report
  • [Publications] Yamada, T., Fujino, T.et al.: "Thromboxane A_2 regulates vascular tone via its inhibitory effect on the expression of inducible nitric oxide synthase"Circulation. 108. 2381-2386 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Xiao, C.-Y., Yuhki, K.et al.: "Prostaglandin E_2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP_4"Circulation. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujino, T., Yuhki, K., et al.: "Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells"Br.J.Pharmacol.. 136. 530-539 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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