A Multiscale In Silico Analysis Identifies Plasma Levels of miR-223-3p as an Emerging Biomarker of Cardiac Response...

Exercise induces a systemic response that involves complex gene regulation influenced by circulating miRNAs, which are post-transcriptional regulators and communication molecules between tissues. Although previous studies have shown that exercise alters plasma miRNA profiles in amateur or highly trained athletes, the impact on Olympic athletes remains unexplored. Therefore, this study aimed to evaluate changes in the whole circulating miRNA profile and their functional implications based on acute exercise and training responses in Olympic medallists. We conducted a study involving four Olympic medallists who completed two maximal aerobic tests during two moments of the Olympic season. Plasma samples were extracted before and after both tests. A total of 752 miRNAs were profiled using high-throughput qRT-PCR, followed by functional characterization via integrated bioinformatics analyses (target prediction, pathway enrichment, and protein interaction network modeling). Our findings revealed two distinct circulating miRNA profiles in response to the maximal aerobic capacity test, depending on training status. Functional in silico analysis across multiple biological scales of the different acute exercise profiles revealed a regulatory shift from broad, canonical coordination to a more fragmented regulatory function. Notably, miR-223-3p was significantly upregulated with acute exercise and downregulated due to training. A correlation between miR-223-3p and maximal heart rate was observed, alongside our in silico analysis describing the association with heart contraction, membrane depolarization, cardiac conduction and atrial cardiac muscle action potential. In conclusion, the specific miRNA profiles identified in Olympic medallists provide new insights into biomarkers of exercise during an Olympic season, introducing the miR-223-3p as a novel indicator of acute exercise and training cardiac exercise adaptations.