New insights into the activin signaling system in pulmonary arterial hypertension (PAH) show that there is a potential prognostic role for the biomarkers activin A and follistatin-like 3 (FSTL3), according to a study published in Circulation. 

Although there is much that we still do not understand about the etiology of PAH, there is enough evidence to suggest that activins act as novel therapeutic targets in this disorder. Guignabert and colleagues thus postulated that certain members of the activin pathway may also function as prognostic biomarkers. 

The research team recruited patients with PAH of 3 subtypes: idiopathic, heritable, and anorexigen-associated PAH. They primarily sought to measure the serum levels of activin A, activin B, the α-subunits of the inhibin proteins A and B, and the antagonists follistatin and FSTL3 in these patients. This was done at baseline and again approximately 3 to 4 months after the initiation of treatment. Control subjects were recruited and underwent the same blood measurements. The research team also analyzed the expression patterns of follistatin, FSTL3, and the others in both groups of individuals. 

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The main outcome of the study was death and/or lung transplantation. The authors then pieced together the real-world clinical outcomes of patients with the levels/expression of members of the activin pathway to determine their value for prognostic assessment. 

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Eighty patients with PAH took part in the trial. Approximately 32.5% of patients died or had lung transplantation, and the median follow-up period was 69 months. An independent external validation cohort identified activin A and FSTL3 as possible prognostic biomarkers for PAH. Both activin A and TSTL3 also yielded important prognostic information even after adjusting for New York Heart Association functional class, the 6-minute walk distance, and N-terminal pro-B-type natriuretic peptide. 

“These findings offer new insights into the activin signaling system in PAH,” the authors concluded. 


Guignabert C, Savale L, Boucly A, et al. Serum and pulmonary expression profiles of the activin signaling system in pulmonary arterial hypertensionCirculation. Published online April 25, 2023. doi:10.1161/CIRCULATIONAHA.122.061501