Quantitative proteomic analysis of the human extracellular vesicle proteome reveals a novel mechanism for tissue cross-talk during exercise

Exercise stimulates the release of a plethora of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognising that many circulating proteins might be packaged in extracellular vesicles (EV), we employed quantitative proteomic techniques to characterise the exercise-induced secretion of EV contained proteins. We observed an increase in circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles, in human arterial blood samples. Pathway analyses revealed significant enrichments in a multitude of biological processes and signalling pathways. Pulse chase and intravital imaging experiments suggest EV-mediated muscle-liver cross talk during exercise. Moreover, by employing arterio-venous balance studies across the contracting human limb, we identified several novel candidate myokines. These data offer a new paradigm by which tissue cross-talk during exercise can exert systemic biological effects