Title: Fatty acid-binding proteins sustain endothelial glycolysis and arterial programming in pulmonary arterial hypertensionProject 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 vascular remodeling and obliterativevascular lesion formation remain unclear. Fatty acid metabolism dysfunction is linked to PAH. Howeverthe mechanistic role of fatty acid metabolism in regulating pulmonary vascular remodeling in thepathogenesis of PAH has not been reported. We hypothesize that endothelial fatty acid-binding proteins4 and 5 (FABP4-5) regulate endothelial glycolysis and arterial programming through HIF-2a/SOX17signaling which contributes to severe vascular remodeling in the pathogenesis of PAH. We will 1) definethe novel role of endothelial FABP4-5 in the pathogenesis of PAH using multiple transgenic animalmodels. 2) delineate the cellular and molecular mechanisms that FABP4-5 induces arterial programmingand pathogenesis of PAH. Completing our proposed study will provide a novel therapeutic strategy forthe effective treatment of PAH in patients.