Circulating microRNAs as emerging cardiac biomarkers responsive to acute exercise

Background: Circulating microRNAs (c-miRNAs) are mediators of intercellular communication with great potential as cardiac biomarkers. The analysis of c-miRNAs in response to physiological stress, such as exercise, would provide valuable information for clinical practice and a deeper understanding of the molecular response to physical activity. Here, we analysed for the first time the acute exercise response of c-miRNAs reported as biomarkers of cardiac disease in a well-characterized cohort of healthy active adults.

Methods: Blood samples were collected immediately before and after (0 h, 24 h, 72 h) a 10-km race, a half-marathon (HM) and a marathon (M). Serum RNA from 10-km and M samples was extracted and a panel of 74 miRNAs analysed using RT-qPCR. c-miRNA response was compared with a panel of nine cardiac biomarkers. Functional enrichment analysis was performed. Pre- and post-M echocardiographic analyses were carried out.

Results: Serum levels of all cardiac biomarkers were upregulated in a dose-dependent manner in response to exercise, even in the absence of symptoms or signs of cardiac injury. A deregulation in the profiles of 5 and 19 c-miRNAs was observed for 10-km and M, respectively. Each race induced a specific qualitative and quantitative alteration of c-miRNAs implicated in cardiac adaptions. Supporting their discriminative potential, a number of c-miRNAs previously associated with cardiac disease were undetectable or stable in response to exercise. Conversely, "pseudo-disease" signatures were also observed.

Conclusions: c-miRNAs may be useful for the management of cardiac conditions in the context of acute aerobic exercise.

Translational aspects of the work: Circulating microRNAs could offer incremental diagnostic value to established and emerging cardiac biomarkers, such as hs-cTnT or NT-proBNP, in those patients with cardiac dysfunction symptoms after an acute bout of endurance exercise. Furthermore, circulating miRNAs could also show "pseudo-disease" signatures in response to acute exercise. Clinical practitioners should be aware of the impact caused by exercise in the interpretation of miRNA data.