MicroRNA in blood could be PAH marker in congenital heart disease

Higher miR-3591-5p levels seen in CHD patients with moderate, severe PAH

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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High levels of a small RNA molecule in the blood may be a marker of pulmonary arterial hypertension (PAH) in people with congenital heart diseases, a new study reveals.

The study, “Expression and Diagnostic Value of miR-3591-5p in Patients with Congenital Heart Disease-Associated Pulmonary Arterial Hypertension,” was published in Lung.

PAH is marked by high blood pressure in the vessels that carry blood through the lungs. People with congenital heart disease (CHD), a broad category that encompasses problems with heart structure or function from birth, are at high risk of developing PAH.

MicroRNAs, often abbreviated miRNAs, are small pieces of RNA that regulate gene activity within cells. The impact of these small RNA molecules in human disease is only starting to be understood, but research suggests it could be immense.

“There is evidence that miRNAs are involved in regulating over 30% of the established human genes and nearly all the [disease-driving] processes in humans,” wrote researchers at Nantong University in China, who looked for distinct miRNA profiles in blood samples from people with CHD-related PAH. The study included samples from 110 people with CHD. Fifty didn’t have PAH, 30 had mild PAH, and 30 had PAH that was moderate to severe. Samples from 40 people who didn’t have CHD were included as controls.

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PAH marker in people with CHD

Significantly higher levels of a miRNA molecule, dubbed miR-3591-5p, were seen in those with CHD and moderate to severe PAH than in those with only CHD and the controls. It was also higher in those with CHD and mild PAH, and in those with CHD only, than the controls.

Among the PAH patients, data indicated a positive correlation between levels of miR-3591-5p and measures of mean pulmonary artery pressure. In other words, those with higher levels of this miRNA tended to have higher pressure in the blood vessels of their lungs, indicating more severe PAH. Levels of miR-3591-5p also correlated with other disease-relevant measures, such as the amount of resistance in lung blood vessels.

High miR-3591-5p levels, relative to other blood proteins, could accurately identify 41.7% of patients with PAH and 86% of those who didn’t have PAH. These findings indicate “miR-3591-5p has predictive and diagnostic value for CHD-PAH,” the researchers wrote.

Assessments of biological function indicated miR-3591-5p may play a role in the TGF-beta pathway, a signaling pathway that’s been heavily implicated in PAH.

The study “highlights the potential of miR-3591-5p as a biomarker for the diagnosis and assessment of the severity of PAH in patients with CHD,” wrote the researchers, who emphasized further research is needed to validate these findings.

While largely focused on miR-3591-5p, the researchers said their analysis identified several other promising miRNA molecules as potential markers of PAH. “It is expected that these differential miRNAs will eventually serve as early diagnostic and prognostic indicators in terms of CHD-PAH,” they said.