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. 2024 Aug 5;15:6640. doi: 10.1038/s41467-024-50996-5

Fig. 2. Deletion of GSDME alleviates aPD-1 therapy-induced myocarditis and mitochondrial damage.

Fig. 2

A Morphology of hearts isolated from tumour-bearing WT and Gsdme−/− mice received aPD-1 therapy or control IgG. B Representative hematoxylin & eosin (H&E) staining and amplified images in whole heart section. The infiltrated immune cells were obviously noted in the myocardium of WT mice received aPD-1 therapy (blue dotted-line area). Scale bar, 200 μm. C Representative echocardiograms and quantitative analyses of heart systolic functions, inducing left ventricular ejection fraction (LVEF), LV end systolic volume (LVESV) and LV end diastolic volume (LVEDV) in WT and Gsdme−/− mice received aPD-1 therapy or control IgG. D Running distance and time of WT and Gsdme−/− mice received aPD-1 therapy or control IgG. E Serum concentrations of cTnT, cTnl and CK-MB in WT and Gsdme−/− mice received aPD-1 therapy or control IgG. F The mRNA levels of Tnnt2 (encoding cTnT) and Tnni3 (encoding cTnI) in hearts of WT and Gsdme−/− mice received aPD-1 therapy or control IgG. G Representative staining images of wheat germ agglutinin (WGA, for cardiomyocyte membrane labeling) in heart section and quantitative analysis of cardiomyocyte size in WT and Gsdme−/− mice received aPD-1 therapy or control IgG. DAPI (blue) was used to stain nuclei. Scale bar, 10 μm. H Representative Sirius-Red staining in heart section and quantitative analysis of myocardial fibrosis in WT and Gsdme−/− mice received aPD-1 therapy or control IgG. The red-stained fiber is collagen fibers. Scale bar, 100 μm. I Representative immunoblotting of IL-1β and its mature cleavage form in heart of WT and Gsdme−/− mice received aPD-1 therapy or normal IgG. J Representative transmission electron microscopy (TEM) images and quantitative analysis of mitochondrial damage in heart of WT and Gsdme−/− mice received aPD-1 therapy or control IgG. Scale bar, 5 μm. The data were presented as means ± SEM and analyzed by two-sided unpaired Student’s t-tests. n = 6 biologically independent experiments.