Skip to main content
. Author manuscript; available in PMC: 2016 Jan 1.
Published in final edited form as: Nat Med. 2015 Jun 15;21(7):777–785. doi: 10.1038/nm.3877

Figure 4. Pulmonary hypertension in Bmpr2+/R899X knock-in mice is reversed by BMP9.

Figure 4

(a) Assessment of right ventricular systolic pressure (RVSP) in 6-month-old, naive Bmpr2+/R899X mice (n=21, 11 male, 10 female) and WT littermate controls (n=23, 13 male, 10 female) or with 4 weeks of BMP9 treatment (75 ng/day, i.p., n=10 (9 male, 1 female) for WT and n=11 (9 male, 2 female) for Bmpr2+/R899X; 1-way ANOVA, Tukey’s post test). (b) Right ventricular hypertrophy (Fulton index, ratio of RV weight over LV and septal weight) in the same animals as a (not significant). (c) Quantitative assessment of pulmonary arterial muscularization in the same groups as a. Displayed as a non-, partially- and fully-muscularized arteries as a percentage of total alveolar wall and duct arteries (n=12 (6 male, 6 female) for naïve WT and Bmpr2+/R899X mice; with BMP9 treatment n=3 (2 male, 1 female) for WT and n=5 (3 male, 2 female) for Bmpr2+/R899X; 1-way ANOVA, Tukey’s post test). (d) Representative images of immunohistochemical staining for smooth muscle α-actin in lung sections from WT and Bmpr2+/R899X mice with or without BMP9 treatment. (e) Assessment of RVSP and (f) RV hypertrophy in male 6 month-old WT (n=16), Smad1+/− (n=9), Bmpr2+/R899X (n=10) and compound Bmpr2+/R899X/Smad1+/− heterozygotes (n=10; 1-way ANOVA, Tukey’s post test). (g) Quantification of monolayer permeability at 2 hours post-LPS. (n=3; 1-way ANOVA, repeated measures Tukey’s post test for WT or Bmpr2+/R899X cells; #P<0.05, 1-way ANOVA, Tukey’s post test for all groups). AU: Arbitrary units. (h) Images of lungs isolated from mice injected with 2 mg/kg LPS or vehicle and either 36.79 ng/25g BMP9 or vehicle (all i.p.) 22 hours prior to the i.p. injection of Evans blue dye, which was delivered 2 hours prior to sacrifice. (i) Quantitative assessment of extravascular Evans blue dye in the lungs of the mice described in h (Control: n=7 (5 male, 2 female) for WT, n=9 (4 male, 5 female) for Bmpr2+/R899X; LPS: n=8 (5 male, 3 female) for WT, n=10 (6 male, 4 female) for Bmpr2+/R899X; LPS + BMP9: n=8 (4 male, 4 female) for WT, n=9 (5 male, 4 female) for Bmpr2+/R899X; 1-way ANOVA, Tukey’s post test for WT or Bmpr2+/R899X mice; #P<0.05, 1-way ANOVA, Tukey’s post test for all groups). ***P<0.001, **P<0.01, *P<0.05. Mean +/− SEM.