NAD-dependent Signaling and Pulmonary Vascular Remodeling in PAH

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ABSTRACT Pulmonary arterial hypertension (PAH), a rare, debilitating and fatal disease for which there is currently no available cure. There is compelling evidence that NAD-dependent signaling via NAMPT is a novel and therapeutic target for PAH. To facilitate the translation of current in vivo and in vitro observations on the role of NAMPT dependent signaling in PAH pathobiology, this proposal will explore the hypothesis that the NAMPT/NAD signaling axis regulates physiologic, cellular and molecular pathways in PAH that result in pulmonary vascular remodeling. SA1 seeks to define the role of pulmonary artery endothelial cell NAMPT in the regulation on metabolic reprograming associated with the PH response. SA2 define the role of NAMPT in regulating mitochondrial dynamics in pulmonary artery endothelial cells. SA3 will seek discover and validate biochemical and genetic NAMPT-centric biomarkers of PAH susceptibility and prognosis.