Title: General Capillary to Arterial Endothelial Cell Transition in Pulmonary ArterialHypertensionProject Summary Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonaryvascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophyfailure and premature death. The underlying mechanisms of loss of capillary endothelial cells (ECs) andobliterative vascular lesion formation remain unclear. Our preliminary data showed that arterialprograming was evident in human PAH patients and rodents. We hypothesize that general capillary ECsprogram to arterial ECs through HIF-2-Cdk19/Sox17/Notch4 signaling which contributes to thepathogenesis of PAH. Completing our proposed study will provide a novel therapeutic strategy for theeffective treatment of PAH in patients.