Nature medicine
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Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with obliteration of pulmonary arterioles and formation of plexiform lesions composed of hyperproliferative endothelial and vascular smooth-muscle cells. Here we describe a microRNA (miRNA)-dependent association between apelin (APLN) and fibroblast growth factor 2 (FGF2) signaling in pulmonary artery endothelial cells (PAECs). ⋯ Reconstitution of miR-424 and miR-503 in vivo ameliorated pulmonary hypertension in experimental models. These studies identify an APLN-dependent miRNA-FGF signaling axis needed for the maintenance of pulmonary vascular homeostasis.