Vesicle-Encased MicroRNAs in Blood Circulation May Help Diagnose Cardiac Sarcoidosis

MicroRNAs encased in small vesicles (exosomes) present in blood circulation may help identify sarcoidosis patients at risk of developing cardiac sarcoidosis (CS).

The study “Exosomal MicroRNA for Detection of Cardiac Sarcoidosis” was published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM).

“CS is the second leading cause of sarcoidosis-related death, and young adults are particularly at risk. A contributing factor is failure to detect CS during routine clinical screening, including patient history, physical exam and electrocardiography,” researchers wrote.

Current methods for diagnosing CS include high-resolution cardiac imaging techniques, such as cardiac magnetic resonance (CMR), or fluorine-18 fluorodeoxyglucose-positron emission computed tomography (18 FDG-PET CT). These, however, are not only expensive and difficult to implement on a routine basis, but also carry the risk of radiation exposure.

Increasingly recognized in other diseases is the diagnostic value of circulating biomarkers, i.e., factors that may be associated only with a disease state and are readily available for detection in a patients’ blood sample.

However, “to our knowledge, no circulating biomarker has shown to reliably detect CS,” researchers noted.

A group of RNA molecules, called non-coding RNAs, readily detected in blood circulation have been shown to be useful biomarkers for heart diseases, such as acute myocardial damage. Certain types of non-coding RNAs, called microRNAs, in the blood are frequently found encased in small vesicles called exosomes.

Researchers investigated whether “exosome-derived microRNAs could serve as an informative source of biomarkers for CS.” To this end, they performed a retrospective study with 21 patients who presented both clinical and radiographic evidence of CS. Additionally, two other groups were included: One with 21 sarcoidosis subjects with no evidence of CS (non-CS), and another group with 11 healthy volunteers.

The team extracted exosomes from blood samples collected from participants of all three groups, and analyzed exosome-content for microRNAs.

Researchers found 13 miRNAs whose expression varied between the three groups analyzed. Two particular microRNAs, called miR-7-1-3p and miR-211-5p, were reported previously as biomarkers of ischemic heart disease. Moreover, the levels of expression of these miRNAs were found significantly different between all sarcoidosis patients and healthy controls.

Notably, two microRNAs – miR-32-3p and miR-211-5p – were found to have higher concentrations in the non-CS group when compared to the CS group. A third microRNA, miR-7-1-3p, was found significantly higher in CS patients.

Overall, these findings “suggest that specific exosomal miRNAs could serve as biomarkers of myocardial involvement in patients with sarcoidosis,” researchers said.

However, “further investigation is needed to determine whether exosomal miRNA can reflect changes in cardiac activity (e.g., in response to immune suppression), or whether miRNA markers from exosomes can detect and differentiate other sarcoidosis phenotypes (e.g., neurosarcoidosis),” the researchers concluded.