Aerobic exercise inhibits GSDME-dependent myocardial cell pyroptosis to protect ischemia-reperfusion injury

Figures

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  Fig. 1. Aerobic exercise inhibits myocardial cell pyroptosis by elevating peripheral circulating IGFBP2 levels. A The diagram presents the protocol for the animal model used in the study. B IGFBP2 levels in serum from WT+IR, WT+Exercise+IR, IGFBP2_KO+Exercise+IR, IGFBP2_OE+IR mice measured by ELISA. C Echocardiographic results of each mouse group. D TTC staining results of mouse cardiac tissues from each mouse group. E TUNEL staining results of mouse cardiac tissues from each mouse group. F Western blot analysis of N-GSDME and cleaved-caspase3 in mouse cardiac tissues. G TUNEL staining of cardiomyocytes (IR, IR+IGFBP2). H Western blot detection of N-GSDME and cleaved-caspase3 in cardiomyocytes of each group

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  Fig. 2. The GSDME-dependent myocardial cell pyroptosis mediates heart IR injury. A Echocardiographic results and left ventricular thickness from control mice and GSDMEcKO (GE_cKO) mice. B Triphenyl Tetrazolium Chloride (TTC) staining of heart tissues from control mice and GE_cKO mice. C TUNEL staining results of heart tissues from control mice and GE_cKO mice. D WB results of N-GSDME and cleaved-caspase3 in heart tissues of control mice and GE_cKO mice. E TUNEL staining of WT, GE_sh and GE_OE cardiomyocytes. F Western blot analysis results of N-GSDME and cleaved-caspase3 in WT, GE_sh and GE_OE cardiomyocytes

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  Fig. 3. GSDME is required for the apoptosis of myocardial cells inhibited by IGFBP2 in IR heart. A Echocardiographic assessment results of mouse experimental groups including WT+ IR, GE_CKO+IR, IGFBP2_OE+IR, IGFBP2_KO+IR, IGFBP2_KO+GE_CKO+IR, IGFBP2_OE+GE_CKO+IR. B TTC staining results of mouse cardiac tissues of each mouse group. C TUNEL staining results of mouse cardiac tissues. D Western blot analysis of N-GSDME and cleaved-caspase3 in mouse cardiac tissues. E TUNEL staining of cardiomyocytes in cell experimental groups. F Western blot detection of N-GSDME and cleaved-caspase3 in cardiomyocytes of cell experimental groups

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  Fig. 4. IGFBP2 protects mitochondrial function of myocardial cell by upregulating AKT-GSK3β phosphorylation levels. A Western blot analysis of p-AKT, p-GSK3β, p-VDAC1, AKT, GSK3β, and VDAC1 levels in heart tissue from each mouse experimental group. B Electron microscopy of mouse heart tissue across experimental groups. C Quantification of ROS and MDA levels in mouse heart tissue across experimental groups. D Assessment of inflammatory cytokines and cleaved-caspase 1 levels in mouse heart tissue across experimental groups. E Western blot analysis of cardiomyocytes from various experimental groups showing protein expression levels of N-GSDME, cleaved-caspase3, p-AKT, p-GSK3β, p-VDAC1, AKT, GSK3β, and VDAC1. F Assessment of ROS levels in cardiomyocytes across experimental groups. G Measurement of MDA levels in cardiomyocytes across experimental groups. H Immunofluorescence staining of cardiomyocytes using ER-tracker (red) and Hoechst 33342 (blue) to visualize mitochondrial respiratory function

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  Fig. 5. Phosphorylation of VDAC1 inhibits glucose GSDME-dependent pyroptosis by modulating mitochondrial function. A TUNEL staining of cardiomyocytes in each experimental group. B Western blot analysis of cardiomyocytes from each experimental group showing protein expression levels of N-GSDME, cleaved-caspase3, p-AKT, p-GSK3β, p-VDAC1, AKT, GSK3β, and VDAC1. C Electron microscopy of cardiomyocytes from each experimental group. D Quantification of ROS and MDA levels in cardiomyocytes across experimental groups. E Immunofluorescence staining of cardiomyocytes using ER-tracker (red) and Hoechst 33342 (blue) to visualize mitochondrial respiratory function. F A proposed model for this study