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Title: Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis
Authors: Heymans, Stephane ×
Pauschinger, Matthias
De Palma, Armando
Kallwellis-Opara, Angela
Rutschow, Susanne
Swinnen, Melissa
Vanhoutte, Davy
Gao, Fangye
Torpai, Raimund
Baker, Andrew H
Padalko, Elizaveta
Neyts, Johan
Schultheiss, Heinz-Peter
Van de Werf, Frans
Carmeliet, Peter
Pinto, Yigal M #
Issue Date: Aug-2006
Series Title: Circulation vol:114 issue:6 pages:565-573
Abstract: BACKGROUND: Acute viral myocarditis is an important cause of cardiac failure in young adults for which there is no effective treatment apart from general heart failure therapy. The present study tested the hypothesis that increased expression of the proteinases urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) is implicated in cardiac inflammation, injury, and subsequent failure during Coxsackievirus-B3 (CVB3)-induced myocarditis. METHODS AND RESULTS: First, we showed increased expression and activity of uPA and MMP-9 in wild-type mice at 7 days of CVB3-induced myocarditis. Targeted deletion of uPA, which resulted in reduced MMP activity and cytokine expression or inhibition of MMPs by adenoviral gene overexpression of tissue inhibitor of metalloproteinases-1, decreased cardiac inflammation and reduced myocardial necrosis at 7 days and decreased cardiac fibrosis at 35 days after CVB3 infection. Importantly, loss of uPA or MMP activity prevented CVB3-induced cardiac dilatation and dysfunction, as determined by serial echocardiography. CONCLUSIONS: Loss of uPA or MMP activity reduces the cardiac inflammatory response after CVB3 infection, thereby protecting against cardiac injury, dilatation, and failure during CVB3-induced myocarditis.
URI: 
ISSN: 0009-7322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Laboratory of Virology and Chemotherapy (Rega Institute)
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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