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 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