Photo Credit: ArtemisDiana

Researchers identified several inflammatory circulating proteins that could be useful biomarkers for predicting outcomes in pulmonary arterial hypertension.

Several inflammation-related circulating proteins appear to predict the risk of lung transplantation or death in patients with pulmonary arterial hypertension (PAH), according to a study published in the Journal of the American Heart Association.

“Pulmonary arterial hypertension ultimately leads to right ventricular failure and premature death,” wrote corresponding author Steeve Provencher, MD, MSc, and coauthors. “The identification of circulating biomarkers with prognostic utility is considered a priority.”

The study focused on inflammation-related circulating proteins because chronic inflammation is considered a pathogenic driver of PAH. Specifically, researchers measured plasma levels of 384 inflammatory proteins in 60 patients with PAH and 28 control subjects with normal hemodynamics.

According to the study, the results identified 51 circulating proteins that were significantly overexpressed in the plasma of patients with PAH compared with control subjects. Among them, 17 were initially linked with lung transplantation or death in patients with PAH.

However, after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk scores, and the refined 4-strata risk assessment, only six proteins remained independently associated with lung transplantation or death at the time of diagnosis with PAH:

• CRIM1 (cysteine-rich transmembrane bone morphogenetic protein regulator 1);
• HGF (hepatocyte growth factor);
• FSTL3 (follistatin-like 3);
• PLAUR (plasminogen activator, urokinase receptor);
• CLSTN2 (calsyntenin 2); and
• SPON1 (spondin 1).

Four of the six—namely, CRIM1, PLAUR, FSTL3, and SPON1—showed incremental prognostic value on top of the 2015 European Society of Cardiology/European Respiratory Society guidelines, REVEAL 2.0 risk scores, and the refined 4‐strata risk assessment predictive models.

Western blot analysis revealed that FSTL3 and SPON1 were markedly upregulated in the right ventricle of patients with PAH and in PAH animal models. The finding suggests the stressed right ventricle is a source of circulating FSTL3 and SPON1 in patients with PAH.

“The present study, using high‐throughput proteomic technologies, enabled us to identify potential novel immune‐related plasma biomarkers, which may help improve outcome prediction in PAH if externally confirmed in future studies,” Dr. Provencher and colleagues concluded.