From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.

Abstract

Pulmonary arterial hypertension (PAH) is a severe disorder of the pulmonary vasculature leading to right ventricular failure. This pulmonary vascular remodelling leads to increased pulmonary vascular resistance and high pulmonary arterial pressures. Despite the development of new therapies, many patients continue to experience significant morbidity and mortality. This review offers a comprehensive overview of the current understanding of PAH pathophysiology, with a focus on key mechanisms that contribute to pulmonary endothelial cell dysfunction and the pathological accumulation of pulmonary artery smooth muscle cells, mesenchymal cells and inflammatory cells in the walls of remodelled small pulmonary vessels, three processes central to the progression of PAH. In particular, it highlights recent developments in targeting the activin signalling pathway, a novel therapeutic approach that shows promise in modulating these pathological processes. The review also addresses the ongoing challenges in translating preclinical findings into effective clinical treatments, emphasising the importance of integrating human data with preclinical models and adopting innovative strategies to bridge the gap between research and clinical practice.