Artikel
In chronic myocarditis LV-dysfunction and myocardial fibrosis is associated with an dysregulation in the MMP-system
In chronischer Myokarditis sind LV-Dysfunktion und myokardiale Fibrose mit einer Dysregulation im MMP- System assoziiert
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Veröffentlicht: | 10. August 2005 |
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Introduction: Acute viral myocarditis with viral persistence and ongoing myocardial inflammation can lead to left ventricular dysfunction and dilatated cardiomyopathy. Proinflammatory cytokines with their influence to the MMP/TIMP system and the myocardial cell infiltration play a crucial role in heart failure with induced myocardial collagen turnover, necrosis and fibrosis. The present study investigated inflammation and extracellular matrix alteration in a murine chronic myocarditis model.
Methods: Coxsackie virus B-3 infected and non-infected SWR/J mice (each n=30) were analyzed on day 4, 7 and 28-post infection (each n=10). Hemodynamic parameters were measured in anesthetized, artificially ventilated and closed-chest animals and the mRNA abundance of MMP-3, MMP-8, TIMP-1, IL-1b, TNF-a and CVB-3 was analyzed by RT-PCR. Furthermore total collagen and CD3+ infiltration was measured in paraffin-embedded sections.
Results: CVB-3 infection caused left ventricular dysfunction on 28 days post infection with a significant induced fibrosis. Moreover the MMP-3 and MMP-8 mRNA expression was significantly induced with chronically reduced TIMP-1 mRNA abundance. In addition we found an ongoing inflammation with significantly induced mRNA levels of IL-1b and TNF-a with elevated myocardial CD3 infiltration. Furthermore we have significant correlation between inflammation and matrix-degradation. (*p<0,05 versus Kontrolle (ANOVA-Test)
Conclusion: The induced fibrosis with relevant left ventricular dysfunction like dilatated cardiomyopathy was due to elevated MMPs and reduced levels of TIMP-1 in the chronic phase. Furthermore the ongoing inflammation with chronically elevated inflammatory cytokines and CD3+ cells by nearly complete viral clearance plays an important role.
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