Iron therapies for chronic heart failure and pulmonary arterial hypertension could be devised to directly correct local iron deficiency, enhance iron uptake (by enhancing local IRPs) and retention (by enhancing local HAMP, e.g., using bone morphogenetic protein receptor 2 (BMPR2) ligands for PAH), or to correct downstream changes in metabolism, oxygen sensing (e.g., HIF inhibitors), calcium handling, or vasoconstriction (e.g., endothelin-1 (ET-1) receptor antagonists). This evidence concerns the gene EDN1 and pulmonary arterial hypertension.