ABSTRACT
Mattea Pellerito
Research Assistant
University of Michigan
ann arbor, Michigan, United States
Littermate FXIII+/+, FXIII-/+, and FXIII-/- mice on a C57BL/6 background were used. Mice were subjected to either a complete inferior vena cava (IVC) ligation stasis or an IVC stenosis to create VT. Tissues and thrombi were harvested at 8 days. Tissues were evaluated by immunohistochemistry, trichrome analyses, weight-to-length data, and immunoblotting.
Results: Whereas FXIII+/+ and FXIII+/- mice had similar VT size 8 days after thrombus induction, FXIII-/- mice had significantly smaller VT than FXIII+/+ mice (10.3 vs 18.0 mg/mm; N=9-18, P=0.001). The thrombus architecture was markedly different in the FXIII-/- stasis mice, with little interstitial matrix (Figure). Immunoblotting showed fibrin (0.15 vs 0.44, ratio to B-actin, N=6, P=0.004), laminin (0.0 vs 0.21, N=6, P=0.002), and fibronectin (0.0 vs 1.25, N=6, P=0.004), and CitH3 (a NETs marker) (0.02 vs 4.7, N=6, P< 0.001) were significantly reduced compared with controls. Intra-thrombus proinflammatory monocyte (CCR2+) counts were reduced by 54% (N=4-8, P=0.02), but no difference in neutrophils in FXIII-/- mice was observed as compared with controls. FXIII+/- mice using both VT models showed no significant differences in VT size as compared to controls.
Conclusions: Analyses of cellular and matrix content following VT induction indicate FXIII is a critical factor for VT resolution, likely through both monocyte and matrix interactions. Whether inhibition of FXIII will accelerate fibrinolysis and enhance thrombus resolution warrants further study.