New blood markers show promise for group 2 pulmonary hypertension

Study links microRNAs to disease severity in small group of patients

Written by Marisa Wexler, MS |

A illustration of DNA and its double helix.

Measuring levels of tiny pieces of genetic material in the blood, known as microRNAs, may help identify group 2 pulmonary hypertension (PH), according to a new study.

“We identified a set of circulating [microRNAs] that are differentially expressed in Group 2 PH and correlated with disease severity,” researchers wrote in the study, “Identification of circulating microRNA biomarkers in pulmonary hypertension of group 2 for early detection,” published in Frontiers in Cardiovascular Medicine. 

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What group 2 pulmonary hypertension is and how it’s diagnosed

Group 2 PH refers to pulmonary hypertension — elevated pressure in the blood vessels that carry blood from the heart to the lungs — caused by disease of the left side of the heart, which pumps oxygen-rich blood to the body. As with other types of PH, the gold standard for diagnosis is right heart catheterization, an invasive test that directly measures pressure in the lungs’ blood vessels. Researchers are working to develop less invasive tests that may help with diagnosis.

MicroRNAs, also called miRNAs, are small pieces of RNA, a type of genetic material. Unlike messenger RNA (mRNA), which helps make proteins, microRNAs help control how other genes are turned on or off in cells.

Previous studies suggest that microRNAs are involved in how PH develops and progresses, and changes in their levels may contribute to disease processes.

Study explores blood microRNAs as possible diagnostic markers

In this study, scientists in China investigated whether microRNAs might serve as useful diagnostic markers for group 2 PH. The researchers analyzed microRNA levels in blood samples from 30 men: 10 healthy individuals, 10 with coronary heart disease but no PH, and 10 with coronary heart disease and group 2 PH.

The researchers initially identified hundreds of microRNAs with altered levels, then narrowed these down through several steps. Eleven microRNAs were validated and found to be linked to disease severity, and five showed the strongest associations with key measures of PH severity.

To evaluate how well these five microRNAs could serve as diagnostic markers, the researchers used a statistical measure called the area under the receiver operating curve, or AUC. AUC measures how well a test can distinguish between two groups — in this case, people with or without PH. AUC values range from 0.5 to 1, with values closer to 1 indicating better accuracy.

Four of the five microRNAs showed high accuracy, with AUC values ranging from 0.87 to 0.97. The fifth microRNA performed poorly, with an AUC of 0.55.

“These miRNAs exhibited high diagnostic accuracy, as reflected by their AUC values, suggesting their potential utility as non-invasive biomarkers for Group 2 PH,” the researchers wrote.

Four microRNAs show strong accuracy in identifying disease

The four microRNAs with the highest accuracy were mmu-miR-452-3p_1ss20GA, hsa-miR-1287-5p_R + 1, hsa-miR-10a-3p_R-1, and bta-miR-1246-p5_1ss18AG. Further analyses suggested these microRNAs are linked to biological pathways involved in PH, which the researchers said supports the idea that they could serve as markers of the disease.

The researchers noted this was a small study that included only male participants, and that diagnoses were based on clinical and imaging measures rather than the gold-standard invasive test, so larger and more diverse studies are needed to confirm the findings.

“These miRNAs hold potential as novel diagnostic biomarkers and offer insights into disease mechanisms. Therefore, their therapeutic potential and clinical applicability merit further investigation,” they wrote.