Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training

Non‐technical summary MicroRNA (miRNA) molecules are essential intracellular mediators of numerous biological processes including angiogenesis, inflammation, and mitochondrial metabolism. Recently, it has been shown that miRNAs are secreted into the bloodstream and that circulating miRNAs (c‐miRNAs) may serve important endocrine functions. This study examined plasma profiles of specific c‐miRNAs in healthy competitive athletes at rest and during exhaustive exercise testing, before and after a 90 day period of exercise training. In this setting, we observed four distinct patterns of c‐miRNA response to exercise: (1) c‐miRNAs up‐regulated by acute exhaustive exercise before and after sustained exercise training, (2) c‐miRNAs responsive to acute exhaustive exercise before but not after sustained exercise training, (3) c‐miRNAs responsive only to sustained exercise training, and (4) non‐responsive c‐miRNAs. These findings set the stage for further work aimed at defining the role of c‐miRNAs as fitness biomarkers and physiological mediators of exercise‐induced cardiovascular adaptation. MicroRNAs (miRNAs) are intracellular mediators of essential biological functions. Recently, plasma‐based ‘circulating’ miRNAs (c‐miRNAs) have been shown to control cellular processes, but the c‐miRNA response to human exercise remains unknown. We sought to determine whether c‐miRNAs are dynamically regulated in response to acute exhaustive cycling exercise and sustained rowing exercise training using a longitudinal, repeated measures study design. Specifically, c‐miRNAs involved in angiogenesis (miR‐20a, miR‐210, miR‐221, miR‐222, miR‐328), inflammation (miR‐21, miR‐146a), skeletal and cardiac muscle contractility (miR‐21, miR‐133a), and hypoxia/ischaemia adaptation (miR‐21, miR‐146a, and miR‐210) were measured at rest and immediately following acute exhaustive cycling exercise in competitive male rowers (n= 10, age = 19.1 ± 0.6 years) before and after a 90 day period of rowing training. Distinct patterns of c‐miRNA response to exercise were observed and adhered to four major profiles: (1) c‐miRNA up‐regulated by acute exercise before and after sustained training (miR‐146a and miR‐222), (2) c‐miRNA responsive to acute exercise before but not after sustained training (miR‐21 and miR‐221), (3) c‐miRNA responsive only to sustained training (miR‐20a), and (4) non‐responsive c‐miRNA (miR‐133a, miR‐210, miR‐328). Linear correlations were observed between peak exercise levels of miR