HIF2α neutralization abolished the effect of VEGFR1 on CLG.

VEGFR1 treatment (F) again increased lung volume compared to the vehicle control group (V) (A). The administration of PT-2385, a HIF2α inhibitor, had no effect on lung volume without (I) or with (I+R1) VEGFR1. Compared to the V group, mice in the F group demonstrated increased physical activity as evidenced by increased basic and fine movement count (B and C), decreased rest time (D), and increase walking distance (E). These differences disappeared between the I and I+R1 groups (F-I). On IHC, there was an increased number of proliferating endothelial cells (white arrows) in the F group compared to the remaining 3 groups (J). There was no difference in endothelial proliferation between the I and I+R1 groups. Data are expressed as mean ± standard error (SE).