Abstract 16628: The Uncoupling Protein 2: The New Metabolic Switch in Human Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is characterized by vascular lesions and obstructions of the distal pulmonary arteries (PA). This phenotype is associated with metabolic unbalance known as Warburg effect (enhanced glycolysis/glucose oxidation). In cancer, this metabolic signature accounts for cell proliferation and resistance to apoptosis, through the activation of the hypoxic inducible factor-1 (HIF-1). While a similar metabolic and proliferative/anti-apoptotic phenotype has been described in human PAH, the origin of the Warburg effect remains unknown. Uncoupling proteins UCPs are mitochondrial proteins that short circuit the electrochemical gradient created by the mitochondrial respiratory chain by sustaining an inducible proton conductance. Nonetheless due to their varied tissue distribution and regulation distinct roles have been identified. For instance, UCP2 differs from other UCPs by not exclusively conducting protons, but also pyruvate, which could explain the Warburg effect. We h...