Circulating Activin A, FSTL3 and BMP9 in asymptomatic BMPR2 pathogenic-variant carriers

Extract Pulmonary arterial hypertension (PAH) is characterized by distal pulmonary arteriolar remodelling with a progressive rise in pulmonary vascular resistance (PVR), right-ventricular (RV) dysfunction, and, in the absence of effective therapy, premature death [1]. Pathogenic variants in the BMPR2 gene, which encodes bone morphogenetic protein receptor type II (BMPR-II) represent the most common genetic predisposition to heritable PAH [2]. Beyond BMPR2, overactivation of the pro-proliferative TGF-#x03B2;–activin–nodal axis plays a pivotal role in driving obstructive vascular remodelling in PAH pathogenesis.