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Important role of inflammation on drug induced pulmonary hypertension

Research Project

Project/Area Number 14571261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionMie University

Principal Investigator

SHIMPO Hideto  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70179076)

Co-Investigator(Kenkyū-buntansha) MITANI Yoshihide  Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (60273380)
矢田 公  三重大学, 医学部, 教授 (80093152)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Keywordspulmonary hypertension / p38MAPK / inflammation / remodeling of pulmonary artery / 肺血管再構築 / P38MAPK
Research Abstract

We postulated that inhibition of p38 MAPK with FR 167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats. Rats were divided into four groups : the control group, FR group (daily FR 167653), MCT group (60mg/kg monocrotaline), MCT with FR group (daily FR 167653 after single MCT).
Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT with FR group was lower than in the MCT group. In morphometric analysis the percentage of medial wall thickness and percentage of muscularization in the MCT with FR group were reduced compared with those in the MCT group. P38MAPK activity was significantly attenuated in the MCT with FR group compared with in the MCT group. mRNA levels of tumor necrosis factor α and interleukin 1β were reduced in the MCT with FR group compared with in the MCT group.
Fr-167653 significantly attenuates the expression of cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38MAPK might play a center role of in the molecular events that underline the development and progression of pulmonary hypertension.

Report

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

    (4 results)

All 2004 Other

All Journal Article (3 results) Publications (1 results)

  • [Journal Article] Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats2004

    • Author(s)
      Lu Jun
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery 128・6

      Pages: 850-859

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Specific inhibition of p38 mitogen-activated protein kinase with ER167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.2004

    • Author(s)
      Jun Lu, Hideto Shimpo, Akira Shimamoto, Albert J.Chong, Craig R.Hampton, Denise J.Spring, Masaki Yada, Motoshi Takao, Koji Onoda, Isao Yada, Timothy H Pohlman, Edward D.Verrier
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery 128(6)

      Pages: 850-859

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Specific inhibition of p38 mitogen-activated protein kinase with E R167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.2004

    • Author(s)
      Lu Jun
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery 128・6

      Pages: 850-859

    • Related Report
      2004 Annual Research Report
  • [Publications] Jun Lu, Hideto Shimpo, Akira Shimamoto, Isao Yada, et al.: "Specific inhibition of p38 MAPK with FR167653 attenuates vascular proliferation in monocrotaline induced pulmonary hypertension in rats"Journal of Thoracic and Cardiovascular Surgery. (In press).

    • Related Report
      2003 Annual Research Report

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

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