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Matrix Degradative Enzyme Activities on Cardiac Remodeling in Heart Failure

Research Project

Project/Area Number 14570670
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MAKINO Naoki  Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (60157170)

Co-Investigator(Kenkyū-buntansha) OYAMA Junich  Kyushu University, Kyushu University Hospital at Beppu, Assistant, 大学病院, 助手 (30359939)
門上 俊明  九州大学, 生体防御医学研究所, 助手 (40335980)
小柳 雅孔  九州大学, 生体防御医学研究所, 助手 (00325474)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCardiac Remodeling / Brain Natriuretic Peptide / Cytokines / PPAR-r / NFκ-B / MMP / MMP / 低酸素 / 心筋細胞 / TNF-alpha / TIMP
Research Abstract

The development of congestive heart failure is associated with left ventricular dilation and myocardial remodeling. The matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) activities play a significant role for remodeling of heart. Cardiac fibroblasts (CFs) as well as myocytes produce extracellular matrix proteins and participate in the remodeling of the heart. The brain natriuretic peptide (BNP) is well known as one of markers in heart failure of experimental and clinical situations. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix production. In this study, we examined the production of BNP in neonatal cardiac CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a ELISA assay demonstrated that BNP was secreted into the media and the amount of BNP secretion was significantly augmented by tumor necrosis factor or angiotensin. When CFs was induced at reoxygenation after hypoxia for 24 hour, BNP mRNA expression was observed significantly and inhibited by the pretreatment with PPAR-r agonist (Pioglitazobe). In addition, protein expression of MMP-1, -2, and TLMP-1 was significantly increased in reoxygenation at 3 hours. PPAR-r agonist decreased the levels of expression of collageni, collagen ill, MMP-l, -2, and TIMP-l. In summary, this study reports that BNP is present in cultured CFs and that BNP levels increased at reoxygenation-induced damage of CFs. However, PPAR-r agonist may regulate collagen synthesis and alter MMPs protein levels. These in vitro findings support, a role for BNP as a regulator of myocardial structure via control of cardiac fibroblast function.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Suematsu N, Satoh S, Ueda Y, Makino N.: "Effects of calmodulin and okadaic acid on myofibrillar Ca2+ sensitivity in cardiac myocytes."Basic Res Cardiol.. 97. 137-144 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Suematsu N, Ueda Y, Tsutsui H, Egashira K, Takeshita A, Makino N.: "Post-beta-receptor impairment in the regulation of myofibrillar Ca2+ sensitivity in tachypacing-induced canine failing heart"J Cardiovasc Pharmacol. 39. 88-97 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M., Tsuchida K., Tomita H., Makino N: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor I gene"Atherosclerosis. 162. 77-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction."FASEB J. 16. 1421-1422 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."J.Cardiovasc Pharmacol.. 40. 146-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Ueda Y, Suematsu N, Oyama J, Kadokami T, Sugano M, Yoshikawa Y, Makino N.: "Beneficial effects of angiotensin-converting enzyme inhibition on sarcoplasmic reticulum function in the failing heart of the Dahl rat."Circ J.. 67. 705-711 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Ueda Y, Koyanagi M, Kadokami T, Sugano M, Yoshikawa Y, Makino N.: "Chronic inhibition of Rho kinase blunts the process of left ventricular hypertrophy leading to cardiac contractile dysfunction in hypertension-induced heart failure."J Mol Cell Cardiol.. 35. 59-70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alpha receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Mol Cell Biochem. 258. 57-63 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular Gene Transfer of Soluble Tumor Necrosis Factor-Receptor 1 Activates Vascular Endothelial Growth Factor Receptor and Accelerates Angiogenesis in a Rat Model of Hindlimb Ischemia"Circulation. 109. 797-802 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Makino N, Sugano M, Masutomo K, Hata T, Fushiki S: "Cardiac Remodeling and Heart Failure"Kluwer Academic Publishrs, Boston. 305-317 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suematsu N, Satoh S, Ueda Y, Makino N.: "Effects of calmodulin and okadaic acid on myofibrillar Ca2+ sensitivity in cardiac myocytes."Basic Res Cardiol.. 97. 137-144 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Suematsu N, Ueda Y, Tsutsui H, Egashira K, Takeshita A, Makino N.: "Post-beta-receptor impairment in the regulation of myofibrillar Ca2+ sensitivity in tachypacing-induced canine failing heart."J Cardiovasc Pharmacol.. 39. 88-97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M., Tsuchida K., Tomita H., Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor I Gene."Atherosclerosis.. 162. 162-184 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor I alleviates myocardial infarction."FASEB J.. 16. 1421-1422 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."J. Cardiovasc Pharmacol.. 40. 146-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Ueda Y, Suematsu N, Oyama J, Kadokami T, Sugano M, Yoshikawa Y, Makino N.: "Beneficial effects of angiotensin-converting enzyme inhibition on sarcoplasmic reticulum function in the failing heart of the Dahl rat."Circ J.. 67. 705-711 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh S, Ueda Y, Koyanagi M, Kadokami T, Sugano M, Yoshikawa Y, Makino N: "Chronic inhibition of Rho kinase blunts the process of left ventricular hypertrophy leading to cardiac contractile dysfunction in hypertension-induced heart failure."J Mol Cell Cardiol.. 35. 59-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alpha receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Mol Cell Biochem. 258. 57-63 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular Gene Transfer of Soluble Tumor Necrosis Factor-Receptor 1 Activates Vascular Endothelial Growth Factor Receptor and Accelerates Angiogenesis in a Rat Model of Hindlimb Ischemia"Circulation. 109. 797-802 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Satoh, Y.Ueda, et al.: "Beneficial effects of angiotensin-converting enzyme inhibition on sarcoplasmic reticulum function in the failing heart of the Dah1 rat."Circulation Journal. 67・8. 705-711 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction."FASEB Journal. 16. 1421-1422 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Increased proliferation of endothelial cells with overexpression of soluble TNF-α receptor I gene."Atherosclerosis. 162. 77-84 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL."Journal of Cardiovascular Pharmacology. 40. 146-152 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Intramuscular gene transfer of soluble TNF-alpha receptor 1 activates vascular endothelial growth factor receptor (KDR/flk-1) and accelerates angiogenesis in a rat model of hindlimb ischemia."Circulation. 103. 797-802 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Effects of soluble TNF-alpha receptor 1 on apoptosis induced by oxidized LDL in endothelial cells."Molecular Cellular Biochemistry. 258. 57-63 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Tomita H, Makino N.: "Role of Monocyte Chemoattractant Protein-1 in Cardiovasuclar Remodeling Induced by Chronic Blockade of Nitric Oxide Synthesis"Atherosclerosis. 162. 77-84 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suematsu N, Satoh S, Ueda Y, Makino N.: "Effects of calmodulin and okadaic acid on myofibrillar Ca2+ sensitivity in cardiac myocytes"Basic Res Cardiol. 97. 137-144 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh S, Suematsu N, Ueda Y, Tsutsui H, Egashira K, Takeshita A. Makino N.: "Post-receptor impairment in the regulation of myofibrillar Ca2+ sensitivity in tachypacing-induced canine failing heart"J Cardiovasc Pharmacol. 39. 88-97 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N.: "Related Articles, Links In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction"FASEB J. 16. 1421-1422 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugano M, Tsuchida K, Makino N.: "Related Articles, Linko Nifedipine prevents apoptosis of endothelial cells induced by oxidized low-density lipoproteins"J Cardiovasc Pharmacol. 40. 148-152 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh S, Ueda Y, Koyanagi M, Kadokami T, Sugano M, Makino N.: "Chronic inhibition of Rho kinase blunts the process of left ventricular hypertrophy leading to cardiac contractile dysfunction in hypertension-induced heart failure"J Mol Cell Cardiol. 35. 59-70 (2003)

    • Related Report
      2002 Annual Research Report

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

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