Left ventricular enlargement in coxsackievirus-B3 induced chronic myocarditis--ongoing inflammation and an imbalance of the matrix degrading system.
Enteroviruses, especially Coxsackie B3 virus (CVB-3), cause acute viral myocarditis, but the detailed mechanisms leading to chronic left ventricular dysfunction and dilatation remain elusive. Myocardial tissues of CVB-3 infected and sham infected male swr/J mice were analyzed after hemodynamic evaluation on days 4, 7, and 28 p.i. by RT-PCR, gelatin zymography, ELISA, immunohistochemistry, sirius red staining, and luxol fast blue staining. In the early phase after infection an abnormal diastolic function was the main hemodynamic finding. CVB-3 infection caused impairment of left ventricular function combined with ventricular dilatation 7 and 28days post-infection. These hemodynamic findings were associated with relevant upregulation of different cytokines (IL-1beta, IL-6, IL-10, INF-gamma, and TNF-alpha) in the acute phase with persistent over-expression of IL-6, IL-10, and INF-gamma in the chronic phase. This virus induced myocardial inflammation was linked to a significant induced MMP/TIMP system (MMP-2,-3,-8, TIMP-1, uPA, tPA-mRNA expression, and MMP-2-activity) in the acute and chronic phase leading to imbalance in the MMP/TIMP-ratio at day 28. This imbalance in the MMP/TIMP system was significantly correlated to the development of ventricular dilatation. Viral persistence induces chronic myocardial inflammation and an imbalance of the matrix degrading system, associated with the development of left ventricular dysfunction and dilatation in chronic murine myocarditis.
Rutschow
Susanne
S
Department of Cardiology and Pneumonology, Medizinische Klinik II, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. susannerutschow@gmx.de <susannerutschow@gmx.de>
Leschka
Sebastian
S
Westermann
Dirk
D
Puhl
Kerstin
K
Weitz
Anneke
A
Ladyszenskij
Leonid
L
Jaeger
Sebastian
S
Zeichhardt
Heinz
H
Noutsias
Michel
M
Schultheiss
Heinz-Peter
HP
Tschope
Carsten
C
Pauschinger
Matthias
M
D000818:Animals; D003384:Coxsackievirus Infections / Q000503:physiopathology; D029822:Enterovirus B, Human / Q000235:genetics / Q000302:isolation & purification; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000503:physiopathology* / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8