NOTCH3 and pulmonary arterial hypertension: It restricts the proliferation of PASMCs and restores the phenotype of PH-associated PASMCs, transitioning them from a dedifferentiated to a differentiated state by intervening in the Notch-HEY2 pathway.235 According to Zhang et al. Notch3 signaling activation stimulated pulmonary vascular cell proliferation by SKP2-and Hes1-mediated p27Kip1 reduction during MCT-PAH.237 Heightened expression and transcriptional activity of Notch1 in human PAECs have been demonstrated under hypoxic conditions, contributing to hypoxia-induced cell proliferation.