Document Detail


Inhibition of coagulation factor Xa improves myocardial function during CVB3-induced myocarditis.
MedLine Citation:
PMID:  24533719     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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-infected 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<0.118; CO: fondaparinux 15124±2183 vs saline 8088±1035 [μl/min], p<0.05). Therapy with fondaparinux reduced the activity of MMP-2 (fondaparinux 1.208±0.1247 vs saline 1.565±0.05476, p<0.05). The collagen type I/III ratio as well as the expression of TIMP-1 were comparable in both treatment groups p.i., despite an increased infiltration of macrophages into the hearts of mice treated with fondaparinux 8 d p.i. (CD68+: fondaparinux 494.2±64.73 vs saline 306.9±43.73 [cells/mm2], p<0.05). Anti-inflammatory CD206 positive M2 type macrophages were elevated in the infected hearts after fondaparinux treatment (CD206+: fondaparinux 182.1±18.18 vs saline 111.6±21.07 [cells/mm2], p<0.05), whereas CD80 positive M1 type macrophages were comparable in both groups.
CONCLUSION: In conclusion, selective inhibition of FXa improves the left ventricular function during CVB3-induced myocarditis and seems to be associated with an improved myocardial remodeling. This article is protected by copyright. All rights reserved.
Authors:
Ronny Malz; Alice Weithaeuser; Carsten Tschöpe; Heinz-Peter Schultheiss; Ursula Rauch
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-17
Journal Detail:
Title:  Cardiovascular therapeutics     Volume:  -     ISSN:  1755-5922     ISO Abbreviation:  Cardiovasc Ther     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101319630     Medline TA:  Cardiovasc Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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