Figure 1.

Endothelial Sox17 deficiency induces severe pulmonary arterial hypertension (PAH) with high penetrance in mice. A, Experimental schedule of Sox17 deficiency-induced PAH. Control and Sox17^i∆EC mice were exposed to normoxia or hypoxia for 3 weeks. B–E, Sox17^i∆EC mice exposed to hypoxia displayed typical pathologic features of PAH as shown by increased wall thickness (B) and hypermuscularization of distal pulmonary arterioles (n=50 per group, 5 arterioles in each mice; C), increased lung infiltration of CD11b⁺ cells (number per high power field of lung sections, n=7 for control/normoxic mice and n=8 for other groups; D), and RV hypertrophy measured by Fulton index (n=13 per group; E). F, Sox17^i∆EC/hypoxic mice displayed hemodynamic evidence of PAH, including elevated RV systolic pressure, which was attenuated partially by overexpressing N1ICD in ECs (n=6 for control/normoxic and Sox17^i∆EC/hypoxic mice, n = 5 for Sox17^i∆EC/N1ICD^iOE/hypoxic mice, and n=4 for other groups), and (G) D-shaped left ventricle (LV), which contrasted to normal shape of the LV in control mice. Asterisks and yellow lines indicate left ventricular cavity and endocardial border, respectively. Data are presented as mean±SD. Generalized estimating equation models (B and C), 1-way ANOVA with Scheffé post-test (D and E), and Kruskal-Wallis test with Dunn’s post-test (F) were performed. Multiple comparison was performed between Sox17^i∆EC/hypoxic mice and each other group (F). Scale bar, 2 mm (G). Ctrl indicates control; HPF, high-power field; LV, left ventricle; and RVSP, RV systolic pressure.