gms | German Medical Science

Introduction: Matrix remodeling is a major topic in heart failure. In patients with DCM and ICM is associated with upregulation of a local induction / activation system formed by EMMPRIN (extracellular matrix metalloproteinase inducer; basignin in mice) as inductor of MMP transcription and MT-MMP (membrane-type matrix metalloproteinase) as activator of translated proMMPs. This system could degrade pericellular matrix but also influences the surrounding tissue by inducting and activating mobile MMPs. It is known to be regulated by inflammatory cytokines but seems to be resistant to endogenous inhibitors like TIMP. However, the expression of this system is not yet studied in myocarditis.

Methods: Therefore 8 weeks old BALB/c mice were infected intraperitoneally with 5 x 105 PFU CVB3 (n=14) or sham-infected (n=10). The examination time-point was 10 days after infection. In all mice EMMPRIN, MT1-MMP, MMP-2 and MMP-9 were analyzed by semiquantitative RT-PCR and gelatinolytic activity was measured using zymography. Statistical analysis was performed using one-way ANOVA.

Results: EMMPRIN, MT1-MMP, MMP-2 and MMP-9 mRNA abundance were significantly induced compared to controls. Gelatinolytic activity of MMP-2 was 3.8 fold and of MMP-9 was 15 fold higher in infected mice. Moreover, the mRNA expression of MT1-MMP was significantly correlated to gelatinolytic activity.

Conclusion: The acute phase of viral myocarditis in mice is associated with an upregulation of the EMMPRIN / MT1-MMP system, which leads to an increase in mRNA expression and activity of MMP-2 and MMP-9. Due to its resistence to TIMP this may be responsible for uncontrolled matrix degradation and LV dysfunction.

Figure 1 [Fig. 1]