Original Article
Regulation of collagen degradation in the rat myocardium after infarction

https://doi.org/10.1016/S0022-2828(05)82390-9Get rights and content

Fibrillar collagens, essential for maintaining the structural integrity of the myocardium, are degraded by matrix metalloproteinase (MMP-1). In other tissues collagenolysis is an important component of wound healing. Here we examined collagen degradation in the myocardium after infarction. Collagenase activity, measured by zymography, and expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of metalloproteinase (TIMP) mRNA, detected by Northern blotting and in situ hybridization, in the rat heart 6 h to 28 days after left coronary artery ligation were studied. Sham-operated rats served as controls. Infarcted left ventricle was compared to non-infarcted right ventricle and interventricular septum and to sham-operated tissues. We found a transient increase in collagenase activity in the infarcted left ventricle, which began at day 2 (4.5-fold increase compared to controls), peaked at day seven (6.5-fold increase) and declined thereafter, together with a concomitant increase and contribution in collagenolytic activity of gelatinases (MMP-2 and MMP-9). An increase in collagenase mRNA was not seen until day 7 and only in the infarcted ventricle, while changes in MMP-1 activity or mRNA expression were not observed at remote sites or in sham-operated controls. Transcription of TIMP mRNA was observed at 6 h (two-fold increase) in the infarcted ventricle, peaked on day two after MI (eight-fold increase) and slowly decreased thereafter. No change in TIMP mRNA expression was observed at remote sites or in sham-operated controls. Cells responsible for transcription of MMP-1 and TIMP mRNA were fibroblast-like cells, not inflammatory or endothelial cells. At the site of infarction post-translational activation of latent collagenase (MMP-1) plays a greater role in the wound healing response than transcription of collagenase mRNA. Collagenase mRNA is synthesized when the latent extracellular pool of MMP-1 is reduced through the activation of latent collagenases and gelatinases. TIMP mRNA synthesis is regulated by the activation of MMPs with the balance between collagenase activation and TIMP inhibition determining the amount of collagenolysis in infarcted tissue.

References (55)

  • MurphyG et al.

    Purification and characterization of a bone metalloproteinase that degrades gelatin and types IV and V collagen

    Biochim Biophys Acta

    (1985)
  • OverallCM et al.

    Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor β

    J Biol Chem

    (1989)
  • ShekhoninBV et al.

    Immunofluorescent identification of fibronectin and fibrinogen/fibrin in experimental myocardial infarction

    J Mol Cell Cardiol

    (1990)
  • TyagiSC et al.

    Direct extraction and estimation of collagenase(s) activity by zymography in microquantities of rat myocardium and uterus

    Clin Biochem

    (1993)
  • van KrimpenC et al.

    DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat heart: effects of captopril

    J Mol Cell Cardiol

    (1991)
  • WaterhouseP et al.

    Modulation of translation by the 5′ leader sequence of the mRNA encoding murine tissue inhibitor of metalloproteinases

    J Biol Chem

    (1990)
  • WeberKT

    Cardiac interstitium in health and disease: the fibrillar collagen network

  • WhittakerP et al.

    Stunned myocardium and myocardial collagen damage: differential effects of single and repeated occlusions

    Am Heart J

    (1991)
  • ZhaoM et al.

    Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium

  • BrownPD et al.

    Independent expression and cellular processing of Mr 72 000 type IV collagenase and interstitial collagenase in human tumorigenic cell lines

    Cancer Res

    (1990)
  • CampbellSE et al.

    Ventricle rupture and fibrillar collagen degradation (Abstract)

    Circulation

    (1991)
  • CasscellsW et al.

    Immunohistochemical study of fibronectin in experimental myocardial infarction

    Am J Pathol

    (1990)
  • CaulfieldJB et al.

    The collagen network of the heart

    Lab Invest

    (1979)
  • CaulfieldJB et al.

    A mechanism for cardiac dilatation

    Heart Failure

    (1990)
  • CaulfieldJB et al.

    Cardiac dilatation associated with collagen alterations

    Mol Cell Biochem

    (1992)
  • ChakrabortyA et al.

    Collagenase activity in the normal rat myocardium: an immunohistochemical method

    Histochemistry

    (1989)
  • CharneyRH et al.

    Collagen loss in the stunned myocardium

    Circulation

    (1992)
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    Current address: Department of Pathology, University of Limburg, P.O. Box 616, 6200 MD Maastricht, The Netherlands

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