Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation, which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of idiopathic PAH.

These findings demonstrate that pharmacological inhibition of HIF-2α is a promising novel therapeutic strategy for the treatment of severe vascular remodeling and right heart failure in patients with PAH.