Extended Data Fig. 3: Additional characterization of the role of YAP/TAZ mechanotransduction in preserving aortic wall integrity.
From: YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS–STING
a, Whole mount X-Gal staining in heart and aorta (upper panel) and aortic wall sections (lower panel, Scale bars, 50 µm) of SmmhcCreER; R26-LSL-LacZ mice, either treated with Tamoxifen or Vehicle. Blue signal confirms the inducible and highly specific activity of the Cre driver in vascular smooth muscle cells. b, Representative immunofluorescence staining for alpha-smooth muscle actin (αSMA, upper panel) and YAP/TAZ (lower panel) in the aortic wall of SmmhcCreER; YAPfl/fl; TAZfl/fl mice, showing YAP/TAZ ablation in vascular smooth muscle cells exclusively after Tamoxifen treatment. Scale bar, 10 µm. c, Quantification of medial layer thickness, adventitial layer thickness and elLam fragmentation of mice of the indicated genotypes. Young control are 7-month-old wild-type mice, Old Control are > 21-month-old wild-type mice. Related to Fig. 3a. Data (n = 8 mice for each column) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. d, e, Representative immunofluorescence staining for p-MLC2 (d, Scale bar, 10 µm) and quantification (e) of p-MLC2 levels in the aortic wall of wild-type (WT) and Fbn1C1039G/WT mice of the indicated ages. elLam is elastic lamellae. Quantification data are presented as mean ± s.d. P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. P < 0.0001 in all conditions compared to 3-month-old wild-type mice, except for 3-month-old Fbn1C1039G/WT mice (P = 0.0092). The number of cells analyzed for each mouse strain and age is reported in the corresponding source data file (where n is > 400 for each point). f, Immunoblotting analysis of total FAK and phospho-FAK (p-FAK) in adventitia-denuded aortic samples from wild-type and 7-month-old Fbn1C1039G/WT mice. α-Tubulin (αTUB) served as loading control. Two mice per condition are shown. g, Quantification of medial layer thickness and adventitial layer thickness in aortic sections of wild-type, Fbn1C1039G/WT and Fbn1C1039G/WT + YAP mice, as in Fig. 3f. Data (n = 8 mice for each group) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test.
