Figure 1.

Loss of endothelial BMPR1A leads to pulmonary arterial hypertension. (A) Microarray-based gene expression profile of BMPR1A in human lungs from control and PAH subjects. ***P < 0.0001 (unpaired t-test). (B) Western blot showing BMPR1A expression level in lung ECs from Bmpr1a^iECKO mice with (Bmpr1a^KO) or without (WT) Cre activation. (C) Right ventricular systolic pressure in Bmpr1a^iECKO mice in comparison with control mice (n = 6). (D) The weight of right ventricle is significantly increased in Bmpr1a^iECKO mice (dots) compared with wildtype mice (dots). **P ≤ 0.005 (unpaired t-test). (E) The right ventricular systolic pressure is progressively elevated over 14 weeks in Bmpr1a^iECKO mice (dots) after tamoxifen administration compared with wildtype mice (dots). [*** < 0.0001, **P ≤ 0.005 (unpaired t-test), n = 5]. (F) Immunostaining showing overall αSMA alteration with vibratome section (150 μm thickness). αSMA deposition was significantly elevated in Bmpr1a^iECKO mice (left). Arrowheads indicate αSMA-positive pulmonary perivasculature (scale bar = 2 mm). (G) Confocal images showing CD31 and αSMA Immunostaining in the lung of control (left) and Bmpr1a^iECKO (right) mice (CD31; αSMA; DAPI). Note that αSMA-positive vessels were increased in Bmpr1a^iECKO mice compared with wildtype mice (scale bar = 300 μm). (H) Quantification of αSMA-positive arteries per field in the lungs of control and Bmpr1a^iECKO mice [***P < 0.0001 (unpaired t-test), n = 10]. (I) Haematoxylin and eosin staining showing medial hypertrophy of pulmonary artery in Bmpr1a^iECKO (right) mice (scale bar = 100 μm). (J) Confocal images showing the muscularized and occluded small (<50 μM) arteries (αSMA; CD31; DAPI) in Bmpr1a^iECKO mice (scale bar = 50 μm). (K) Quantification of small αSMA-positive arteries (<50 μM) in the lungs of control and Bmpr1a^iECKO mice [***P < 0.0001 (unpaired t-test), n = 9].