This review highlights recent advances in basic research and novel therapeutic targets, such as sotatercept, for the treatment of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive obliteration of pulmonary arteries. Dysregulated bone morphogenetic protein (BMP) signaling pathway contributes to the development of PAH, and pulmonary vasodilators including endothelin receptor antagonists, phosphodiesterase 5 inhibitors, prostaglandins and soluble guanylate cyclase stimulators, dramatically improve the long-term prognosis. However, there still exist refractory patients who require continuous catecholamine support or lung transplantation, and the development of new treatment strategies targeting molecular mechanisms of PAH is highly anticipated. Sotatercept, a first-in-class activin signaling inhibitor, has recently been approved for the treatment of PAH, and it targets and restores an imbalance in activin-growth differentiation factor and BMP pathway signaling. In addition, treatment strategies targeting peroxisome proliferator-activated receptor-γ signaling, inflammatory and immune systems, DNA damage response and cellular senescence, and growth factor receptors including vascular endothelial growth factor and platelet-derived growth factor receptors, are being devised. In this review, we briefly summarize the recent advances in basic research paving the way for the development of more effective treatments for PAH and their potential in clinical therapeutic applications.
Fujiwara et al. (2025) studied this question.