Since AKT activation is associated with the development of PAH [5,6,7] and DLL4/NOTCH1, like BMPR2 [31] and PPARγ [32], appear to be protective [33,34], the noncanonical crosstalk and interdependent regulation of these pathways were investigated in healthy and BMPR2-silenced PAECs, as well as in the lungs of patients with heritable PAH (HPAH) and IPAH. Here, DLL4 is linked to idiopathic pulmonary arterial hypertension.