HIF-1α is predominantly expressed in PASMCs, HIF-2α is chiefly found in PAECs, and HIF-3α is primarily expressed in pulmonary fibroblasts.125 Mutations in HIF-2α have been shown to enhance PAH in both murine models and human patients,126,127 and HIF-2α may exert a significant influence on the pathogenesis of PAH, whereas HIF-1α is likely to mainly contribute to disease progression and persistence.128 In sum, HIF-2α emerges as a crucial driving factor in the early stages of the disease, with transitional interactions with HIF-1α. This evidence concerns the gene EPAS1 and pulmonary arterial hypertension.