Related Experiment Video
Updated: May 3, 2026
Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures
Published on: March 12, 2018
Inhibition of coagulation factor Xa improves myocardial function during CVB3-induced myocarditis
Ronny Malz1, Alice Weithauser, Carsten Tschöpe
1Centrum für Herz- und Kreislaufmedizin, Medizinische Klinik II, Charité - Universitätsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany.
Insights
Pharmacological inhibition of Factor Xa (FXa) using fondaparinux improved cardiac function in mice with coxsackievirus B3 (CVB3)-induced myocarditis. This treatment also reduced matrix metalloproteinase-2 activity and modulated macrophage infiltration, suggesting improved myocardial remodeling.
Area of Science:
- Cardiovascular Research
- Virology
- Coagulation and Thrombosis
Background:
- Myocarditis, often induced by coxsackievirus B3 (CVB3), involves inflammation linked to coagulation activation.
- Coagulation Factor Xa (FXa) plays a key role by activating matrix metalloproteinases (MMPs), which influence tissue remodeling.
Purpose of the Study:
- To investigate the impact of pharmacological FXa inhibition on cardiac function, inflammation, and remodeling in a mouse model of CVB3-induced myocarditis.
Main Methods:
- Mice with CVB3-induced myocarditis were treated with the FXa inhibitor fondaparinux or saline.
- Cardiac function was assessed using a microconductance pressure catheter.
- Immunohistochemistry, real-time PCR, and zymography were used to evaluate immune cell infiltration, cytokine expression, and MMP activity.
Main Results:
- Fondaparinux treatment significantly improved left ventricular function (dPdtmax, SV, CO) compared to controls.
- FXa inhibition reduced MMP-2 activity.
- Fondaparinux treatment increased the infiltration of CD68+ macrophages and specifically CD206+ M2-type macrophages, while M1-type macrophages remained comparable.
Conclusions:
- Selective FXa inhibition with fondaparinux enhances left ventricular function in CVB3-induced myocarditis.
- This improvement is associated with favorable myocardial remodeling, potentially mediated by altered macrophage polarization and reduced MMP activity.
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 < 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 was comparable in both infection groups postinfectionem (p.i.), despite an increased infiltration of macrophages into the hearts of mice treated with fondaparinux 8 days p.i. (CD68+: fondaparinux 494.2 ± 64.73 vs. saline 306.9 ± 43.73 [cells/mm(2) ], P < 0.05). Anti-inflammatory CD206-positive M2-type macrophages were increased in the infected hearts after fondaparinux treatment (CD206+: fondaparinux 182.1 ± 18.18 vs. saline 111.6 ± 21.07 [cells/mm(2) ], 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.
More Related Videos
Related Concept Videos
01:14Myocarditis III: Medical Management
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:29Venous Thrombosis III: Interprofessional Care
01:18Endocarditis III: Medical Management
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:21Myocarditis I: Introduction