Inhibition of PHD2 Induces Endothelial-to-Mesenchymal Transition in Pulmonary Vascular Endothelial Cells

RATIONALEPulmonary arterial hypertension (PAH) is a fatal disease that predominantly affect young women. Enhanced proliferation and/or reduced apoptosis of pulmonary vascular endothelial cells (PVEC) contribute to the concentric pulmonary vascular wall thickening and intraluminal obliteration in small pulmonary arteries in patients with PAH. However, the precise pathogenic mechanisms by which PVEC contribute to the formation of intimal lesions is not fully understood. Endothelial-to-mesenchymal transition (EndMT) may convert slowly grown PVEC to highly proliferative myofibroblasts and contribute to pulmonary vascular remodeling in PAH. We recently reported that EndMT of lung microvascular endothelial cells (LMVEC) from patients with PAH was associated with prolyl hydroxylase domain 2 (PHD2) downregulation and that mice with endothelial specific deletion of phd2 or egln1 developed severe pulmonary hypertension (PH) under normoxic conditions. In this study, we further investigate the mechanism by which PHD2...