Fig. 7: Pharmacological inhibition of sGC or PRKG reverts aortopathy in Marfan syndrome.
From: Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO
a Experimental design. 14-week-old MFS mice were treated daily for 21 days with 20mg/kg/day ODQ. Longitudinal ultrasound and BP analysis (Eco-BP) was performed at the indicated times (empty triangles). b Plasma cGMP at 21 d (n = 8 WT mice, n = 10 MFS mice, and n = 9 ODQ-treated MFS mice). c Representative pVASP-S239 immunofluorescence (red) in mouse aortic sections. Yellow dashed lines delineate the lumen boundary. IgG staining served as a negative control. Scale bar, 50 µm. d Quantification of pVASP-S239 immunofluorescence in aortic sections from 10 untreated WT mice (−), 10 MFS mice, and 9 MFS mice treated with 20 mg/kg/day ODQ for 21 d. IgG staining served as a negative control. Scale bar, 50 µm. b, d Data are mean ± s.e.m. Each data point denotes an individual mouse. Differences were analyzed by one-way ANOVA with Tukey’s post-hoc test (p-values are shown). e, f Systolic BP (e) and maximal AsAo and AbAo (f) diameter at the indicated times (n = 5 mice each for untreated and ODQ-treated MFS groups; n = 7 mice for WT group). Data are mean ± s.e.m. **P < 0.01, ***P < 0.001, and ****P < 0.0001 (versus WT mice); ##P < 0.01, ###P < 0.001, and ####P < 0.0001 (versus untreated MFS) by repeated-measurements two-way ANOVA with Tukey’s post-hoc test. g Experimental design. 14-week-old MFS mice were treated daily for 7 days with 2 µmol/kg/day KT5823 and monitored for aortic dilation and BP before treatment and 3 d and 7 d post-treatment. h Representative pVASP-S239 immunofluorescence (red) in mouse aortic sections. Yellow dashed lines delineate the lumen boundary. IgG staining served as a negative control. Scale bar, 50 µm. i Quantification of pVASP-S239 immunofluorescence in aortic sections from untreated WT mice (−) (n = 5), MFS mice (n = 5), and MFS mice treated with 2 µmol /kg/day KT5823 for 7 d (n = 7). Data are shown relative to untreated WT mice as mean ± s.e.m. Each data point denotes an individual mouse. Differences were analyzed by one-way ANOVA with Tukey’s post-hoc test (p-values are shown). j, k Systolic BP (j) and maximal AsAo and AbAo (k) diameter at the indicated times (n = 10 for untreated WT group; n = 8 per each MFS group). Data are mean ± s.e.m. ***P < 0.001 and ****P < 0.0001 (versus WT), #P < 0.05 and ##P < 0.01 (versus untreated MFS) by repeated-measurements two-way ANOVA with Tukey’s post-hoc test. Source are provided in the Source Data file.
