Differential Regulation of miRNA and Protein Profiles in Human Plasma-Derived Extracellular Vesicles via Continuous Aerobic and High-Intensity Interval Training.

Both continuous aerobic training (CAT) and high-intensity interval training (HIIT) are recommended to promote health and prevent diseases. Exercise-induced circulating extracellular vesicles (EX-EVs) have been suggested to play essential roles in mediating organ crosstalk, but corresponding molecular mechanisms remain unclear. To assess and compare the systemic effects of CAT and HIIT, five healthy male volunteers were assigned to HIIT and CAT, with a 7-day interval between sessions. Plasma EVs were collected at rest or immediately after each training section, prior to proteomics and miRNA profile analysis. We found that the differentially expressed (DE) miRNAs in EX-EVs were largely involved in the regulation of transcriptional factors, while most of the DE proteins in EX-EVs were identified as non-secreted proteins. Both CAT and HIIT play common roles in neuronal signal transduction, autophagy, and cell fate regulation. Specifically, CAT showed distinct roles in cognitive function and substrate metabolism, while HIIT was more associated with organ growth, cardiac muscle function, and insulin signaling pathways. Interestingly, the miR-379 cluster within EX-EVs was specifically regulated by HIIT, involving several biological functions, including neuroactive ligand-receptor interaction. Furthermore, EX-EVs likely originate from various tissues, including metabolic tissues, the immune system, and the nervous system. Our study provides molecular insights into the effects of CAT and HIIT, shedding light on the roles of EX-EVs in mediating organ crosstalk and health promotion.