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The study investigated whether activin pathway members could serve as biomarkers for pulmonary arterial hypertension (PAH). Serum levels of activin A, activin B, α-subunit of inhibin A and B proteins, and the antagonists follistatin and follistatin-like 3 (FSTL3) were measured in patients with newly diagnosed PAH. The study found that activin A and FSTL3 were associated with transplant-free survival in PAH patients. The study also confirmed the prognostic values of activin A and FSTL3 in an independent external validation cohort. Histological analyses showed a nuclear accumulation of the phosphorylated form of Smad2/3, higher immunoreactivities for ACTRIIB, ALK2, ALK4, ALK5, ALK7, Cripto, and FSTL3 in vascular endothelial and smooth muscle layers, and lower immunostaining for inhibin-α and follistatin. Overall, the findings offer new insights into the activin signaling system in PAH and highlight activin A and FSTL3 as potential biomarkers for PAH.
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