Fig. 1: Deficiency or overexpression of GSDMD alleviates or aggrevates DOX-induced cardiotoxic injury.

A Kaplan–Meier test showing the overall survival rates of WT and GSDMD-KO mice treated with saline or DOX. N = 10 for Control groups and n = 20 for DOX groups. B Serum of CK-MB and cTnT release detected by Elisa. N = 3–6 per group. Ejection fraction (EF) of four different groups measured by echocardiography. N = 7–9 per group. C Epifluorescence microscopy of WGA and ROS. N = 10–11 per group. D TUNEL assay in myocardium treated with vehicle or DOX co-staining with cTnT (scale bar: 200 μm). N ≥ 6 per group. E Western blots of GSDMD-FL, GSDMD-N, Cleaved-caspase 3 (Cleaved cas3), BAX, IL-18, IL-1β, and β-actin proteins from vehicle-treated control and DOX-treated hearts in the absence and presence of GSDMD. N = 6 per group. F Survival rates of DOX-treated mice and respective sham mice in adeno-associated virus serotype 9 (AAV9-GSDMD-OE) mice or negative control respectively. N = 10 for Control groups and n = 20 for DOX groups. G, H Serum concentrations of CK-MB and cTnT, respectively. N = 3–6 per group. I Ejection fraction (EF) measured by echocardiography. N = 8–10 per group. J WGA (scale bar: 100 μm) and ROS staining (scale bar: 200 μm) detected by epifluorescence microscopy. N = 10 for WGA groups and n = 11 for ROS groups. K Apotosis of myocardium by TUNEL staining co-stained with cTnT (scale bar: 200 μm). N = 10 per group. L Detection of GSDMD, Cleaved-caspase 3 (Cleaved cas3), BAX, and β-actin proteins levels by western blot. N = 6 mice per group. Data are depicted as the mean ± SEM. Statistical significance was determined by one-way and two-way ANOVA with a post hoc Holm–Sidak test, ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.