Inhibition of Coagulation Factor Xa Improves Myocardial Function During CVB3‐Induced Myocarditis

Summary Introduction Myocarditis is induced by coxsackievirus B3 (CVB3). Myocardial inflammation is tied to the activation of coagulation. Coagulation factor (F) Xa, a central player in coagulation, activates matrix metalloproteinases (MMP), which modulate the remodeling. Aims In this study, we inve...

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Bibliographic Details
Published in:Cardiovascular therapeutics 2014-06, Vol.32 (3), p.113-119
Main Authors: Malz, Ronny, Weithauser, Alice, Tschöpe, Carsten, Schultheiss, Heinz‐Peter, Rauch, Ursula
Format: Article
Language:English
Subjects:
Animals
Coxsackievirus Infections - blood
Coxsackievirus Infections - drug therapy
Coxsackievirus Infections - physiopathology
Coxsackievirus Infections - virology
Cytokines - genetics
Cytokines - metabolism
Disease Models, Animal
Enterovirus B, Human - pathogenicity
Factor Xa
Factor Xa - metabolism
Factor Xa Inhibitors - pharmacology
Fondaparinux
Inflammation
Inflammation Mediators - metabolism
Male
Matrix Metalloproteinase 2 - metabolism
Mice, Inbred C57BL
Myocarditis
Myocarditis - blood
Myocarditis - drug therapy
Myocarditis - physiopathology
Myocarditis - virology
Polysaccharides - pharmacology
Remodeling
RNA, Messenger - metabolism
Ventricular Function, Left - drug effects
Ventricular Remodeling - drug effects
Viral Load
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Summary:Summary Introduction Myocarditis is induced by coxsackievirus B3 (CVB3). Myocardial inflammation is tied to the activation of coagulation. Coagulation factor (F) Xa, a central player in coagulation, activates matrix metalloproteinases (MMP), which modulate the remodeling. Aims In this study, we investigated the effects of pharmacological FXa inhibition on myocardial function, inflammation, and remodeling during a CVB3‐induced myocarditis. Methods and Results Immune cells and matrix proteins were detected by immunohistochemistry. The expression of cytokines was measured by real‐time PCR and the activity of MMP‐2 by zymography. Left ventricular function was analyzed using microconductance pressure catheter. Treatment with the FXa inhibitor fondaparinux led to an improved left ventricular function in CVB3‐induced mice compared to saline‐treated controls (dPdtmax: fondaparinux 4632 ± 499.6 vs. saline 3131 ± 374.0 [mmHg/s], P = 0.0503; SV: fondaparinux 33.19 ± 4.893 vs. saline 19.32 ± 2.236 [μL], P 
ISSN:1755-5914
1755-5922
DOI:10.1111/1755-5922.12069