Role of cytokines in cardiac fibrosis and exercise

During acute sympathetic stress, the overeactivation of β-adrenergic receptors (β-ARs) caused cardiac fibrosis, by triggering inflammation and cytokine expression. It is unknown whether exercise training inhibited acute β-AR overactivation-induced cytokine expression and cardiac injury. Here, we reported that running exercise inhibited cardiac fibrosis and improved cardiac function in mice treated by isoproterenol, a β-AR agonist. Cytokine antibody array revealed that exercise prevented the expression changes of most cytokines induced by isoproterenol. Specifically, 18 ISO-upregulated and 3 ISO-downregulated cytokines belonged to six families (eg. chemokine) were prevented. A further KEGG analysis of these cytokines revealed that Hedgehog and Rap1 signaling pathways were involved in the regulation of cytokine expression by exercise. The expression changes of some cytokines that were prevented by exercise were verified by ELISA and real-time PCR. In conclusion, running exercise prevented the cytokine changes following acute β-AR overactivation and therefore attenuated cardiac fibrosis. 10-weeks male C57BL/6 mice were divided into 4 groups (n=4/group), untreated group (Ctrl goup), Running exercise for 6 weeks (Run goup), sedentary group with acute sympathetic stress induced by isoproterenol (Sed+ISO group), and ISO group with running exercise pretreatment (Run+ISO group). 144 cytokines expression were detected by Cytokine Antibody Array.