Abstract 16456: Loss of β-Arrestin 1-Mediated VEGFR3 Signaling Promotes the Development of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by inflammatory and remodeling of pulmonary arterioles, leading to right ventricular (RV) failure and death. Signaling through transmembrane receptors, such as the prostacyclin and type A endothelin receptors, is known to be important in the development of PAH and many of these receptors serve as drug targets. The multifunctional adapter proteins β-arrestin 1 (βarr1) and 2 (βarr2) regulate signaling by G protein-coupled receptors (GPCRs) and other transmembrane receptors, although the physiological importance of this regulation in different disease states is unknown. Recently, we have found that βarr1 knockout (KO) mice develop worse PAH and RV dysfunction in response to hypoxia exposure. Surprisingly, we found that the major signaling abnormalities in the lungs of these mice was not associated with GPCR signaling, but with signaling through the vascular endothelial growth factor receptor 3 (VEGFR3): there was a signifi...