Figure 6.

Smooth muscle cell Cxcr4 mediates smooth muscle cell proliferation and pulmonary hypertension development. (A and B) Inhibition of hypoxia-induced pulmonary hypertension in mice with tamoxifen-induced smooth muscle cell–specific disruption of Cxcr4 (C4^iMyh) in contrast to wild-type (WT) littermates. Three weeks following hypoxia challenge, right ventricular systolic pressure was assessed and then RV/(LV + S) ratio was calculated for determination of right ventricular hypertrophy. (C and D) Quantitative evaluation of Russel-Movat pentachrome staining showing attenuation of vascular remodeling (pulmonary artery [PA] wall thickness) in hypoxia-challenged Cxcr4^iMyh mice compared with Cxcr4^f/f WT mice. PAs with a diameter of 20–200 μm were quantified. (E and F) Quantification of α-SMA⁺ vessels demonstrating inhibited muscularization of distal pulmonary vessels in hypoxia-challenged Cxcr4^iMyh mice compared with WT mice. After 3 weeks of exposure to hypoxia, mouse lungs were collected and processed for immunostaining with anti–α-SMA antibody (red). Nuclei were counterstained with DAPI (blue). Arrows point to muscularized distal pulmonary vessels. **P < 0.01 and ***P < 0.001. (A, B, D, and F) One-way ANOVA. Scale bars: (C) 100 μm; (E) 50 μm. RV/(LV + S) = right ventricle versus left ventricle plus septum; RVSP = right ventricular systolic pressure; SMA = smooth muscle actin.