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THE PATHOGENESIS OF LEFT VENTRICULAR STIFFNESSIN CARDIOMYOPATHIES : ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY.

Research Project

Project/Area Number 07670819
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka Medical College

Principal Investigator

HAYASHI Tetsuya  Osaka Medical College, Department of Medicine, Assistant proffesor, 医学部, 助手 (30257852)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsCardiomyopathy / Stiff heart / Collagen / Immunohistochemistry / Electron microscopy / Matrix metalloproteinase / Remodeling / Zymography / 拘束型心筋症 / 心筋生検 / 細胞外マトリックス
Research Abstract

To clarify the etiology of left ventricular stiffness in cardiomyopathies, the following studies were conducted. (1) On the right ventricular endomyocardial biopsy specimens, the subtypes of collage I,III and IV were analyzed ant the expression of MMP-1 and 2 werestudies semiquantitatively (graded from 0 to 3+) in 14 cases of restrictive cardiomyopathy (RCM), 21 of hypetrophic cardiomyopathy (HCM) and 23 of dilated cardiomyopathy (DCM) by immuno-light and electron microscopy. Furthermore, the MMP-2 activity measured by zymography in 7 KCM 10 DCM cases were comparted with the normal control (n=5) obtained at the bypass surgery. Immunohistochemically, type III collagenincreased remarkably in RCM and HCM,whereas type I and IV collagen was prominent in DCM.The immunoreactivity ageinst MMP-1 was positive along collagen fibrils and in some fibroblasts both in HCM and DCM.The MMP-1 tended to increase as the reactivity against type I and III collagen was prominent. On the other hand, the MMP-2 … More and its activity measured by zymography were prominent in DCM.(2) To elucidate the three dimensional architecture of cardiocytes, collagen and elastic fibers, fifteen autopsied hearts (4 RCM,1obstructuve HCM,3 DCM,2 myocardial infarction, OMI and 5 normal hearts without cardiacdisease) and 3 surgical materials (2 obstructive HCM and 1OMI) were studied by scanning electron microscopy. In RCM and HCM,the cardiocytes were bizarrely shaped and branching, and were irregularly connected with one another. The most striking features in RCM was the thickened perimysium in which collagen bundles of less than 5 mum formed reticular networks together with an increased amount of elastic fibers, which were very similar to those in HCM.On the other hand, in DCM and OMI,endomysium and perimysium were both thickened but the elastic fibers was small in amount. Furthermore, in the perimysium of DCM and OMI,collagens were often organized into thick bundles up 20 mum which ran along the longitudinal axis of neighboring cardiocytes. The above findings suggest that 1) increased reticular networks, which were supposed to be type III colllagen, and elastic elements play an important role as the cause of left ventricular stiffness in RCM and HCM,2) the increased collagen type I reflects the replacement fibrosis in DCM,and 3) MMP appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in cardiomyopathies. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Tetsuya Hayashi: "Ultrastr uctural and lmmunohi stochemical Study of Collagen Types and Matrix Met allopr oteinase in Patients with 1 di opathic Restrictive Car diomy opathy" Japanese Cir culation Journal. 60. 510 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 寺崎文生: "拘束型心筋症における心筋の光顕、電顕、免疫組織学的検討" 循環器科. 39. 396-397 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Manatsu Satoh: "Molecular Genetics of Familial Restrictive Car diomyopathy" Journal of Molecular and Cellular Car diology. 28. A332 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Okabe: "Intercellular connections between laterally apposed cardiocytes are reduced in number by remodeling of cell junctions in aged spontaneously hypertensive rats:Scanning and transmission electron microscopic study" Japanese Cir culation Journal. 60. 435 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Okabe: "Does angiotensin converting enzyme inhibitor restore the remodeling of collahgen arvhitecture to normal in cardiachypertriphy in spontaneously hypertensive rats?" Japanese Cir culation Journal. 59. 423 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Okabe: "Effect of angiotensin II type 1 receptor antagonist, E4177, on myocardial fibrosis in spontaneously hyper tensive rats:Scanning electron microscopic study" Japanese Cir culation Journal. 60. 482-483 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tetsuya Hayashi: "Remodelling of Collagen and Matrix Metalloproteinase Activity in Car diomy opathies" Journal of Molecular and Cellular Car diology. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岡部眞: "加齢・高血圧における心筋細胞結合リモデリング:高血圧自然発症ラットを用いた微細構造学的検索" 心筋の構造と代謝(六法出版社). 253-260 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayashi T,Terasaki F,Hirota Y,Okabe M,Shimomura H,Deguchi H,Kitaura Y,Kawamura K: "Ultrastructural and immunohistochemical study of collagen types and matrix metalloproteinase in patients with idiopathic restrictive cardiomyopathy." Jpn Circ J. 60. 510 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoh M,Harada H,Hiroi S,Nunota S,Terasaki F,Hayashi T,Hirota Y,Kawamura K,Kimura A: "Molecular genetics of familial restrictive cardiomyopathy." J Mol Cell Cardiol. 28. A332 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okabe M,Terasaki F,Kimpara T,Hayashi T,Shimomura H,Kawamura K: "intercellular connections between laterally apposed cardiocytes are reduced in number by remodeling of cell junctions in aged spontaneously hypertensive rats : scanning and transmission electron microscopic study" Jpn Circ J. 60. 435-436 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okabe M,Kimpara T,Terasaki F,Hayashi T,Kawamura K: "Does abgiotensin converting enzyme inhibitor restore the remodeling od collagen architecture to normal in cardiac hypertrophy in spontaneously hypertensive rats?" Jpn Circ J. 59. 423 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okabe M,Terasaki F,Hayashi T,Shimomura H,Kawamura K: "Effect of angiotensin II type 1 receptor antagonist, E4177, on myocardial fibrosis in spontaneously hypertensive rats : scanning electron microscopic study." Jpn Circ J. 60. 482-483 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Terasaki F,Hayashi T,Shimomura H,Deguchi H,Hirota Y,Kitaura Y,Kawamura K: "An ultrastructural and immunohistochemical study on the myocardium in patients with restrictive cardiomyopathy. (In Japanese)" Junkankika. 39. 396-397 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okabe M,Terasaki F,Kimpara T,Shimomura H,Hayashi T,Imamura K,Kawamura K: Remodeling of intercellular jinctions of left ventricular cardiocytes in aged spontaneously hypertensive rats : an ultrastructural study. (In Japanese). Roppoushuppansha, 253-260 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayashi T,Sohmiya K,Okabe M,Terasaki F,Kawamura K: Remodelling of collagen and matrix metalloproteinase activity in cardiomyopathies.J Mol Cell Cardiol, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tetsuya Hayashi: "Ultrastructur al and lmmunohistochemical Study of Collagen Types and Matrix Metalloproteinase in Patients with ldiopathic Restrictive Cardiomyopathy" Japanese Circulation Journal. 60. 510- (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 寺崎文生: "拘束型心筋症における心筋の光顕、電顕、免疫組織学的検討" 循環器科. 39. 396-397 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Manatsu Satoh: "Molecular Genetics of Familial Restrictive Cardio omyopathy" Journal of Molecular and Cellular Cardiology. 28. A332 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Okabe: "Intercellular connections between laterally appoesed cardiocytes are reduced in number by remodeling of cell junctions in aged spontaneously hypertensive rats : Scanning and transmission electron microscopic study" Japanese Circulation Journal. 60. 435 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Okabe: "Effect of angiotensin II type 1 receptor antagonist,E4177,on myocardial fibrosis in spontaneously hyper tensive rats : Scanning electron microscopic study" Japanese Circulation Journal. 60. 482-283 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tetsuya Hayashi: "Remodelling of Collagen and Matrix Metalloproteinase Activity in Cardiomy opathies" Journal of Molecular and Cellular Cardiology. (発表予定).

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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