Extended Data Fig. 9: Neutrophil elastase induces fibrin degradation and endothelial damage during thromboinflammation resolution in the thromboinflammation-on-a-chip model.

a, Timeline for studying the role of neutrophil elastase in thromboinflammation under the 10 ng ml⁻¹ TNF condition. Representative 3D confocal microscopy Z-stack images and a bright field image demonstrate that the human neutrophil elastase inhibitor BAY 85-8501 blocks fibrin degradation and prevents endothelial detachment. b, Timeline for studying the role of neutrophil elastase and endogenous tPA in thromboinflammation under the 1 ng ml⁻¹ TNF condition. Representative 3D confocal microscopy Z-stack images show that the human neutrophil elastase inhibitor BAY 85-8501 and antifibrinolytic drug 6-aminocaproic acid together block fibrin degradation. c, Timeline for studying the role of endogenous tPA in thromboinflammation under the 1 ng ml⁻¹ TNF condition. Representative 3D confocal microscopy Z-stack images show that antifibrinolytic drug 6-aminocaproic acid alone does not block fibrin degradation. d, Quantitative analysis of fibrin shows that inhibition of human neutrophil elastase by BAY85-8501 significantly reduces fibrin degradation on Day 7 post-thromboinflammation compared to the control without inhibitor under the 10 ng ml⁻¹ TNF condition. e, Quantitative analysis of fibrin shows that inhibition of human neutrophil elastase significantly reduces fibrin degradation post-thromboinflammation under the 1 ng ml⁻¹ TNF condition, whereas the antifibrinolytic drug 6-aminocaproic acid alone does not. [n = 4 biologically independent replicates. Data are presented as mean values +/− SD. p values were calculated using two-way ANOVA with Šídák correction (d), or with Dunnett correction (e)].

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