Background
Although the concept of immunothrombosis has established a link between inflammation and thrombosis, the role of inflammation in the pathogenesis of deep vein thrombosis remains to be fully elucidated. Further, although various constituents of venous thrombi have been identified, their localizations and cellular and molecular interactions are yet to be combined in a single, multiplexed analysis. Objectives: The
Conclusions
We observe a key role for VWF in the pathogenesis of inflammation-associated venous thrombosis while providing a more comprehensive insight into the molecular interactions that constitute the architecture of venous thrombi.
Methods
We combined the murine inferior vena cava stenosis model of deep vein thrombosis with the lipopolysaccharide model of endotoxemia. We also performed a proof-of-concept study of imaging mass cytometry to assess the feasibility of this approach in analyzing the structural composition of thrombi.
Results
We found that lipopolysaccharide-treated mice had significantly higher incidences of venous thrombosis, an effect that was mitigated when VWF was inhibited using inhibitory αVWF antibodies. Our detailed structural analysis also showed that most thrombus components are localized in the white thrombus regardless of endotoxemia. Moreover, although endotoxemia modulated the relative representation and interactions of VWF with other thrombus constituents, the scaffolding network, comprised VWF, fibrin, and neutrophil extracellular traps, remained largely unaffected. Conclusions: We observe a key role for VWF in the pathogenesis of inflammation-associated venous thrombosis while providing a more comprehensive insight into the molecular interactions that constitute the architecture of venous thrombi.