Serological biomarkers for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) were identified in a recent study published in Biomedicines.

The 2 microRNAs (miRNAs), miR-26 and miR-let-7d, were found to have lower levels in patients with SSc who had developed PAH (SSc-PAH) than in patients who had not developed PAH (SSc-noPAH). When adjusting for age and removing patients suspected of possibly developing PAH during the study, lower miR-26 and miR-let-7d levels were found to be correlated with patients having PAH (P =.045 and P =.011, respectively), using a partial Spearman’s Rho correlation.

The study also found that the levels of miR-26 and miR-let-7d were significantly correlated with a number of inflammatory markers including complement component 3, C-reactive protein, and immunoglobulin Gs (2 and 4).


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“These data suggest that there is an association between low expression of miR-26 and miR-let-7d and the PAH complication and that there is a correlation between these miRNAs, and parameters associated with inflammation and complement activation,” the authors said.

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Bioinformatic techniques were also utilized to identify gene ontology (GO) annotation targets of miR-26 and miR-let-7d. Many of the identified annotations were related to myofibroblast cells, and the linkages suggest that these miRNAs may also be involved in the regulation of the transforming growth factor-beta pathway. Also, GO-annotations implicated that both miRNAs were involved in cytokine signaling including miR-26 linked to IL18R1 and IRF4 while miR-let-7d was linked to IL-10 and CCR7.

Individually, miR-26 may also be involved in blood vessel morphogenesis and cell motility processes while miR-let-7d may be involved in myofibroblast and endothelial cell proliferation as well as endothelial cell apoptosis. The lower levels of miR-26 and miR-let-7d also coincided with fibroblast differentiation into myofibroblasts.

A total of 25 patients with SSc-noPAH and 12 patients with SSc-PAH were included in the study. A small group of patients with SSc-noPAH had worsening arterial pressure (n=3) during the study and 1 patient developed PAH. These patients had miRNA levels similar to the SSc-PAH group at the beginning of the study but had other parameters such as lung function, similar to the SSc-noPAH group, and were categorized as SSc with suspected PAH.

“These results suggest that low levels of miR-let-7d and miR-26 miRNAs that characterize SSc-PAH patients, can be detected in SSc-noPAH patients even before pulmonary pressure rises. Despite this interesting observation, the limited number of patients (4) does not allow unequivocal conclusions to be drawn,” the authors concluded.

Reference

Zaaroor Levy M, Rabinowicz N, Yamila Kohon M, et al. MiRNAs in systemic sclerosis patients with pulmonary arterial hypertension: markers and effectors. Biomedicines. 2022;10(3):629. doi:10.3390/biomedicines10030629