Collagen degradation in a murine myocarditis model: relevance of matrix metalloproteinase in association with inflammatory induction

Publication

Collagen degradation in a murine myocarditis model: relevance of matrix metalloproteinase in association with inflammatory induction

Journal Paper/Review - Nov 1, 2002

Li Jun, Schultheiss Heinz-Peter, Zeichhardt Heinz, Spillmann Frank, Poller Wolfgang, Kobalz Ursula, Noutsias Michel, Reichenbach Florian, Rutschow Susanne, Husmann Lars, Leschka Sebastian, Tschope Carsten, Schwimmbeck Peter Lothar, Pauschinger Matthias

Units

Radiologie und Nuklearmedizin

PubMed

12393094

Citation

Li J, Schultheiss H, Zeichhardt H, Spillmann F, Poller W, Kobalz U, Noutsias M, Reichenbach F, Rutschow S, Husmann L, Leschka S, Tschope C, Schwimmbeck P, Pauschinger M. Collagen degradation in a murine myocarditis model: relevance of matrix metalloproteinase in association with inflammatory induction. Cardiovasc Res 2002; 56:235-47.

Type

Journal Paper/Review (English)

Journal

Cardiovasc Res 2002; 56

Publication Date

Nov 1, 2002

Issn Print

0008-6363

Pages

235-47

Brief description/objective

OBJECTIVE: Myocardial collagen degradation is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs). The possible relevance of MMPs in association with the inflammatory induction was investigated in a murine coxsackievirus B3 myocarditis model. METHODS: Hearts from viral infected and sham-infected BALB/c mice were analyzed by semi-quantitative RT-PCR, picrosirius red staining, Western blot analysis, and immunohistochemistry. RESULTS: In viral infected mice, both mRNA and protein abundance for collagen type I remained unaltered. In addition, picrosirius red staining showed the unchanged total collagen content. However, degraded soluble fraction of collagen type I protein was increased. Moreover, the mRNA abundance for MMP-3 and MMP-9 was upregulated, whereas the mRNAs for TIMP-1 and TIMP-4 were downregulated, respectively. The upregulation of MMP-3/MMP-9 and downregulation of TIMP-4 were confirmed at the protein level, and were associated with significantly increased mRNA levels of interleukin 1beta, tumor necrosis factor-alpha, transforming growth factor-beta1 and interleukin-4. CONCLUSION: The increment of MMPs in the absence of counterbalance by TIMPs may lead to a functional defect of the myocardial collagen network by posttranslational mechanisms. This may contribute significantly to the development of left ventricular dysfunction in murine viral myocarditis. The inflammatory response with induction of cytokines may mediate the dysregulation of the myocardial MMP/TIMP systems.