Low-intensity exercise training increases systolic function of heart and MHCII low cardiac resident macrophages

Physical activities have beneficial effects on cardiovascular health, although the specific mechanisms are largely unknown. Cardiac resident macrophages (cMacs) and the distribution of their subsets are critical regulators for maintaining cardiovascular health and cardiac functions in both steady and inflammatory states. Therefore, we investigated the subsets of cMacs in mice after lowintensity exercise training to elucidate the exercise-induced dynamic changes of cMacs and the benefits of exercise for the heart. The mice were subjected to treadmill running exercise five days per week for five weeks using a low-intensity exercise training protocol. Low-intensity exercise training resulted in a suppression of body weight gain in mice and a significant increase in the ejection fraction, a parameter that represents the systolic function of the heart. Low-intensity exercise training induced the alterations in the transcriptome of the heart, which are associated with muscle contraction and mitochondrial function. Furthermore, low-intensity exercise training did not alter the number of lymphocyte antigen 6 complex, locus C1 (Ly6c)(-) cMacs but instead remodeled the distributions of Ly6c(-) cMac subsets. We observed an increase in the percentage of major histocompatibility complex class II (MHCII)(low) cMacs and a decrease in the percentage of MHCIIhigh cMacs in the heart after low-intensity exercise training. Therefore, the benefits of exercise for cardiovascular fitness might be associated with the redistribution of cMac subsets and the enhancement of the ejection fraction.