Effective treatments for PAH will require detailed knowledge of molecular aetiology

Abstract

Therapies for idiopathic pulmonary arterial hypertension will need to address the underlying molecular defects, or they will be incapable of halting progression. Identification of the familial PAH gene, BMPR2, and determinants of penetrance in families with BMPR2 mutation, has provided a mechanism for discovering this underlying aetiology not just in those with BMPR2 mutation, but in all patients. These studies suggest that the fundamental defects are in cytoskeletal organization, energy metabolism, and inflammation, with mode of estrogen metabolism acting as the most significant modifier. A detailed understanding of these defects, and a determination of the correct points for intervention, will be required to produce effective treatments for idiopathic PAH.