Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise

Fig. 1. Potential roles of different types of cells in cardiac response to exercise. The schematic depicts ways that exercise may confer its cardiac effects working through distinct cell lineages and molecular pathways. In cardiomyocytes, exercise increases the expression of the transcriptional co-regulator CITED4 and downregulates the long noncoding RNA lncExACT1, increasing available miR-222 and decreasing its transcriptional target, DCHS2. These effects contribute to hypertrophic and proliferative cardiomyocyte responses to exercise. Exercise-induced upregulation of CITED4 in cardiomyocytes negatively regulates cardiac fibroblast activation via cross-talk mediated in part by the miR-30d family and miR-222. In fibroblasts themselves, exercise inhibits myofibroblast activation via Mt1/Mt2 and fibrosis via AMPK, while also inhibiting pathologic fibrosis in ischemic injury, aging, and diabetes through modulation of renin-angiotensin signaling. In hematopoietic stem cells, aerobic exercise exerts a cardioprotective effect by reducing hematopoietic stem cell recruitment of leukocytes to the heart, thereby attenuating cardiac inflammation. Cardiac endothelial cells are both key regulators…