Researchers found that the plasma concentration of soluble receptor for advanced glycation end products (sRAGE) is a sensitive and accurate biomarker for adult pulmonary arterial hypertension (PAH).

They concluded that sRAGE “has comparable diagnostic accuracy to the established heart failure biomarker [N-terminal prohormone of brain natriuretic peptide] and shows even better performance in the distinction between mild PAH and controls.”

Patients with connective tissue disease-associated PAH and idiopathic PAH showed higher levels of sRAGE than healthy control individuals (3332 ± 321.6 pg/mL vs 3044 ± 215.2 pg/mL vs 1766 ± 121.9 pg/mL, respectively; P <.01).

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In addition, sRAGE plasma concentrations correlated with the World Health Organization (WHO) functional class in both adult PAH subtypes. In particular, the study authors reported a significant increase in the plasma levels of sRAGE in the functional class II+III (P <.001) compared to controls.

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Besides plasma concentrations, Diekmann et al analyzed sRAGE expression in lung tissues. They found that the relative messenger RNA expression of RAGE (AGER) was 2.1-fold higher in the whole lung tissues of end-stage idiopathic PAH patients (n=7) than in lung transplantation donor controls (n=9, P <.05).

RAGE was particularly observed in the intima, media, and adventitia of obliterated distal pulmonary arteries and in perivascular cells in the outer adventitia of a patient with end-stage idiopathic PAH.

In contrast to the findings in adult PAH patients, the study authors did not find significant differences in plasma sRAGE concentrations between children with (n=10) and without (n=10) PAH. However, the pediatric cohort presented with higher plasma sRAGE concentrations than the adult cohort.

To date, this was the largest study (n=120) to address sRAGE in PAH and the first to assess sRAGE plasma concentrations in adult patients with connective tissue disease-associated PAH.


Diekmann F, Chouvarine P, Sallmon H, et al. Soluble receptor for advanced glycation end products (sRAGE) is a sensitive biomarker in human pulmonary arterial hypertension. Int J Mol Sci. 2021;22(16):8591. doi:10.3390/ijms22168591