SUMMARY Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart’s capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotype were identified, including HIPK1 and Homeobox-1. Inhibition of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in response to exercise, while reducing markers of cardiomyocyte proliferation. Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant to adverse cardiac remodeling and dysfunction after ischemic injury. These studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth and proliferation in the adult mammalian heart and show that it is sufficient to protect the heart against adverse remodeling.

Exercise has long been considered an essential element for sustaining cardiovascular health. A vast literature of clinical studies suggests that exercise serves as an effective intervention for the primary and secondary prevention of cardiovascular disease, although the optimal nature, intensity, and duration of exercise for maximizing these cardiovascular benefits remain unclear. On a molecular level, exercise induces physiologic growth of the heart primarily by driving cardiomyocyte hypertrophy, notably through the interconnected IGF-1-PI3K-AKT1 and C/EBPβ-CITED4 pathways. Here, we explore the range of clinical evidence supporting the cardiovascular benefits of exercise and outline the molecular pathways that play major roles in regulating these protective effects.

MIS is a promising marker for malnutrition inflammation assessment and an independent predictor of long-term mortality in Chinese PD patients.

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