Fig. 4

S100A9-deficient mice are partially protected against systemic inflammation and left ventricular dysfunction during endotoxemia. Endotoxemia was induced in wild-type or S100A9^−/− C57Bl/6NrJ mice by intraperitoneal injection of 5 mg/kg LPS. In the ABR-238901-treated group, the S100A9^−/− mice received 30 mg/kg ABR-238901 intraperitoneally at 0h and 6h post-LPS. Echocardiography was performed at baseline, 6 h and 24 h. Mice were sacrificed at 24 h for plasma collection and cytokines were measured in plasma using multiplex bead assay. A–C Left ventricular ejection fraction, stroke volume and cardiac output presented as serial measurements over time, with the corresponding area under the curve (AUC). D Heatmap of changes in plasma cytokines in wild-type and S100A9^−/− mice with and without ABR-238901 treatment, expressed as Z-scores. E Individual plasma cytokine and chemokine levels. Statistical testing of echocardiographic parameters over time was performed using repeated-measures 2-way ANOVA with Fisher’s LSD Test. P-values reflect differences between treatment groups over time. Symbols reflect the difference between the treatment groups at the respective time point. Statistical differences between 3 groups were assessed with 1-way ANOVA with Fisher’s LSD Test or Kruskal–Wallis test, following normality assessment with Shapiro–Wilk test. *, S100A9^−/− versus WT; *P < 0.05, **P < 0.01, ***P < 0.001; †, S100A9^−/− + ABR versus WT; † P < 0.05, †† P < 0.01, ††† P < 0.001; WT, wild-type; ABR, ABR-238901; AUC, area under curve; LVEF, Left ventricular ejection fraction; LVSV, Left ventricular stroke volume; LVCO, Left ventricular cardiac output. Data is represented as mean ± SD. N = 5–8 per group