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Oxidative stress in heart failure

Research Project

Project/Area Number 10670656
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

KAWASHIMA Seinosuke  Kobe University, Kobe University Hospital, Lecturer, 医学部・附属病院, 講師 (10177678)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Mitsuhiro  Kobe University, School of Medicine, Professor, 医学部, 教授 (40135794)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsoxidative stress / antioxidant / heart failure / viral myocarditis / endothelin / cardiac hypertrophy / MAP kinase / 肥大 / p42 / p44MAPキナーゼ / 一酸化窒素 / 心筋炎
Research Abstract

We investigated the role of oxidative stress on the pathogenesis of failing heart.
1)In coksacckievirus-induced viral myocarditis in mice, we examined the effects of purobucol (PB), an antioxidaive drug, on the process of myocardial damage. In PB-treated virus-infected mice, superoxide production and activity of inducible NO synthase in the heart were decreased compared with those in non-treated virus-infected mice. Reduction in these inflammatory mediators in PB-treated animals were associated with attenuated activation of the redox-sensitive transcriptional factor, NFκB, in the heart. Along with these improvements, the mortality after virus infection was reduced in PB-treated mice. On the other hand, we could not find the improvement of the process of myocardial damage by PB-treatment in failing heart after myocardial infarction. Therefore, the extent of participation of oxidative stress in the pathophysiology of failing heart may differ depending on the
2)The intracellular signal transduction in endothelin (ET)-induced cardiomyocyte hypertrophy was investigated. In cultured neonatal rat cardiomyocytes, endothelin induced increases in protein synthesis, fetal gene expression and sarcomere arrangement. In association with these changes, ET induced activations of both p42/p44MAP(ERK1/2) kinase and p38 MAP kinase. Inhibition of ERK1/2 activation by pharmacological inhibitors and the dominant negative mutant of MEK blocked hypertrophic response to ET. However inhibition of p38 MAP kinase is necessary for ET-induced cardiomyocyte hypertrophy.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(18 results)

All Other

All Publications (18 results)

  • [Publications] Yoshitaka Ohashi: "Hypotension and Reduced Nitric Oxide-elicited Vasorelaxation in Transgenic Mice Overexpressing Endothelial Nitric Oxide Synthase"The Journal of Clinical Investigation. 102. 2061-2071 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nobutaka Inoue: "Stretch force on vascular smooth muscle cells enhances oxidation of LDL via superoxide production"American Journal of Physiology. 278. H1928-H1932 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomomi Ueyama: "Endothelin-a activates p38 mitogen-activated protein kinase via endothelin-A receptor in rat myocardial cells"Molecular and Cellular Biochemistry. 199. 119-124 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Azumi Hiroshi: "Expression of NADH/NADPH oxidase p22 phox in human coronary arteries"Circulation. 100. 1494-1498 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomoya Yamashita: "Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxidase synthase"Circulation. 101. 931-937 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shigeto Takeuchi: "Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC"Biochemical and Biophysical Research Communication. 269. 97-102 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshitaka Ohashi: "Hypotension and Reduced Nitric Oxide-elicited Vasorelaxation in Transgenic Mice Overexpressing Endothelial Nitric Oxide Synthase"The Journal of Clinical Investigation. 102. 2061-2071 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nobutaka Inoue: "Stretch force on vascular smooth muscle cells enhances oxidation of LDL via superoxide production"American Journal of Physiology. 278. H1928-H1932 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomomi Ueyama: "Endothelin-1 activates p38 mitogen-activated protein kinase via endothelin-A receptor in rat myocardial cells"Molecular and Cellular Biochemistry. 199. 119-124 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Azumi Hiroshi: "Expression of NADH/NADPH oxidase p22 phox in human coronary arteries"Circulation. 100. 1494-1498 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomoya Yamashita: "Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxidase synthase"Circulation. 101. 931-937 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shigeto Takeuchi: "Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC"Biochemical and Biophysical Research Communication. 269. 97-102 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomomi Ueyama: "Endothelin-1 activates p38 mitogen-activated protein kinase via endothelin-A receptor in rat myocardial cells"Mollecular and Cellular Biochemistry. 199. 119-124 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Azumi Hiroshi: "Expression of NADH/NADPH oxidase p22 phox in human coronary arteries"Circulation. 100. 1494-1498 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomoya Yamashita: "Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxidase synthase"Circulation. 101. 931-937 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeto Takeuchi: "Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC"Biochemical and Biophsical Research Communication. 269. 97-102 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshitaka Ohashi: "Hypotension and Reduced Nitric Oxide-elicited Vasorelaxation in Transgenic Mice Overexpressing Endothelial Nitric Oxide Synthase." The Journal of Clinical Investigation. 102. 2061-2071 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nobutaka Inoue: "Stretch force on vascular smooth muscle cells enhances oxidation of LDL via superoxide production." American Journal of Physiology. 278. H1928-H1932 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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