These novel findings demonstrate extensive crosstalk between the DLL4/NOTCH1 and BMPR2/PPARγ networks in the regulation of AKT, supporting the development of strategies to activate DLL4/NOTCH1/PPARγ and/or inhibit AKT signaling for the treatment of pathologic vascular remodeling in PAH. The gene discussed is DLL4; the disease is pulmonary arterial hypertension.