The Basic Science of Metabolism in Pulmonary Arterial Hypertension

Abstract

Pulmonary hypertension (PH) encompasses a group of progressive and incurable cardiopulmonary disorders characterized by pulmonary vascular remodeling and increased mean pulmonary artery pressure leading to right heart failure. Emerging data suggest a common etiology for the reported diverse molecular and physiological abnormalities observed in the pulmonary vasculature: the metabolic theory of PH. This theory proposes that aberrations in metabolism and mitochondrial function are a major underlying cause for the cellular and organ level PH phenotype. Additionally, the metabolic theory of PH provides a rationale for the observed metabolic defects in other organs and systems outside of the pulmonary vasculature, including the right ventricle (RV), immune system, and skeletal muscle. However, whether these metabolic changes are driving disease and the timing and extent of these aberrations are still unknown. This review highlights: 1) key examples of metabolic alterations in the pulmonary vasculature, RV, inflammatory cells, and skeletal muscle; 2) examples of promising therapeutic interventions directly modifying metabolism; and 3) key remaining questions about the role of metabolic remodeling in PH.