Viral myocarditis and coagulopathy: increased tissue factor expression and plasma thrombogenicity

S Antoniak, U Boltzen, A Riad… - Journal of molecular and …, 2008 - Elsevier
S Antoniak, U Boltzen, A Riad, A Kallwellis-Opara, M Rohde, A Dörner, C Tschöpe
Journal of molecular and cellular cardiology, 2008Elsevier
We investigated the effects of viral infection on the Tissue Factor (TF) expression and activity
in mice within the myocardium to understand the increased thrombosis during myocarditis.
Mice were infected with coxsackie virus B3 and the hearts were collected at day 4, 8 and 28
post infection (pi). The myocardial TF expression and cellular activity as well as plasma
activity were analyzed from CVB3 infected mice by western blot, chromogenic factor Xa
generation assay, in situ staining for active TF and immunohistochemistry. In addition to the …
We investigated the effects of viral infection on the Tissue Factor (TF) expression and activity in mice within the myocardium to understand the increased thrombosis during myocarditis. Mice were infected with coxsackie virus B3 and the hearts were collected at day 4, 8 and 28 post infection (p.i.). The myocardial TF expression and cellular activity as well as plasma activity were analyzed from CVB3 infected mice by western blot, chromogenic factor Xa generation assay, in situ staining for active TF and immunohistochemistry. In addition to the TF expression, hemodynamic parameters were measured during the time course of infection. Furthermore, we analyzed myocardial tissues from patients with suspected inflammatory cardiomyopathy. The TF protein expression was maximally 5-fold elevated 8 days p.i. in mice and was still increased on day 28 p.i. (P<0.001 vs. non-infected controls). Alterations in TF expression were associated with fibrin deposits within the myocardium. The TF pathway inhibitor protein expression in the myocardium did not alter during myocarditis. Active cellular TF co-localized with CD3 positive cells and VCAM-1 positive endothelial cells in the myocardium. The TF expression was positively correlated with the amount of infiltrating CD3- and Mac3-positive cells (Spearman-Rho ρ=0.749 P<0.0001 for CD3+ and ρ=0.775 P<0.0001 for Mac3+; N=35). Increased myocardial TF expression was associated with a 2-fold elevated plasma activity (P<0.05 vs. non-infected controls). In the human hearts, the TF expression correlated positive with an endothelial cell activation marker (ρ=0.523 P<0.0001 for CD62E; N=54). Viral myocarditis is a hypercoagulative state, which is associated with an increased myocardial TF expression and activity. Upregulation of TF contributes to a systemic activation of the coagulation cascade.
Elsevier