Resolution of inflammation in pulmonary arterial hypertension, the influence of sex-An IUPHAR immunopharmacology committee review.

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease with limited treatment options. Sex differences are apparent in PAH, specifically in the pathophysiology, prognoses and pharmacological responses of patients. Inflammation and its resolution, which often differ between sexes, are dysregulated in chronic inflammatory conditions such as PAH. Inflammation is yet to be directly targeted by available PAH therapies despite its association with poor patient outcomes. Emerging research highlights the resolution of inflammation, an active process that restores tissue homeostasis, as a therapeutic avenue for treating chronic inflammatory diseases. This review encompasses the key pro-resolving ligands and G protein-coupled receptors involved in the active resolution of inflammation. We explore their dysregulation in PAH and evaluate their therapeutic potential, with a focus on how sex-specific immune responses may influence both preclinical findings and clinical outcomes. Signalling pathways involved in the resolution of inflammation present many therapeutically relevant targets for the development of novel PAH therapies.