Fig. 8: Senolytic therapy ameliorates AAA pathologies in mice with VSMC-specific rescue of GSDME.
From: GSDME-dependent pyroptosis drives abdominal aortic aneurysm via promoting vascular senescence
A SA-β-gal staining of the AAA lesion aorta tree of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of dasatinib plus quercetin (D + Q) or vehicle control. The AAA lesion vasculatures were blue-stained. B Flow cytometry of p16-positive senescent cells in a-SMA+ cells from AAA lesion vasculatures of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. C Flow cytometry of p21-positive senescent cells in a-SMA+ cells from AAA lesion vasculatures of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. D Representative morphology and quantitative analyses of maximal abdominal aortic diameter and aorta weight in GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. E Comparison of the incidence of large P-AAA in GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. The reported numbers (50, 48, 47, and 47 for the four groups) represent the cumulative use across multiple experimental procedures (molecular assays, flow cytometry, histopathology, and survival analyses). F The mRNA expression of SASP factors (Il-1β, Il-6, and Ccl2) in lesion vasculature of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. G Representative H&E staining in lesion vasculature of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. H Representative EVG staining and elastin degradation score in lesion vasculature of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. Representative immunofluorescence staining and quantitative analysis of CCL2 (I) and MMP2 (J) in lesion vasculature of GsdmeStop/Stop and GsdmeSR mice treated by senolytic therapy of D + Q or vehicle control. Data were presented as mean ± SEM. N = 6 biological replicate unless indicated. Chi-squared test was performed in (E), and Unpaired Student’s t-tests were used in other panels. P-AAA, PPE + BAPN-induced AAA.
