Project 2: Despite major advances in understanding PAH in recent decades, safe, effective and tolerable therapies remain elusive. The metabolic syndrome (central obesity, insulin resistance, high blood pressure and hyperlipidemia—fats in the blood) has been implicated in PAH. Treating the downstream consequences of insulin resistance in the pulmonary vasculature is a new approach to effective intervention against this highly mortal disease. This project will study the role of insulin resistance in pulmonary arterial hypertension and determine if therapies to treat insulin resistance will improve pulmonary arterial hypertension.