Regulation of collagen degradation in the rat myocardium after infarction

Jack P.M. Cleutjens, Jagannadha C. Kandala, Eduardo Guarda, Ramareddy Guntaka, Karl Weber

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1281-1292
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number6
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Matrix Metalloproteinases
Infarction
Myocardium
Collagenases
Collagen
Tissue Inhibitor of Metalloproteinases
Messenger RNA
Heart Ventricles
Gelatinases
Matrix Metalloproteinase 1
Wound Healing
Fibrillar Collagens
Tissue Inhibitor of Metalloproteinase-1
Northern Blotting
In Situ Hybridization
Ligation
Coronary Vessels
Endothelial Cells
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Regulation of collagen degradation in the rat myocardium after infarction. / Cleutjens, Jack P.M.; Kandala, Jagannadha C.; Guarda, Eduardo; Guntaka, Ramareddy; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 27, No. 6, 01.01.1995, p. 1281-1292.

Research output: Contribution to journalArticle

Cleutjens, Jack P.M. ; Kandala, Jagannadha C. ; Guarda, Eduardo ; Guntaka, Ramareddy ; Weber, Karl. / Regulation of collagen degradation in the rat myocardium after infarction. In: Journal of Molecular and Cellular Cardiology. 1995 ; Vol. 27, No. 6. pp. 1281-1292.
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