Exercise Training After Myocardial Infarction Enhances Endothelial Progenitor Cells Function via NRG-1 Signaling

Vascular regeneration after myocardial infarction (MI) is essential to improve myocardial ischemia, delay post-infarction ventricular remodeling, and improve the long-term prognosis of MI. Endothelial progenitor cells (EPCs) play important roles in the functional repair and homeostatic maintenance of the vascular endothelium. Exercise training stimulates EPC mobilization and increases the number of circulating EPCs, which has beneficial effects on the restoration of vascular integrity and hemodynamic reconstitution. After post-MI exercise training, cardiac function, the myocardial infarct area, and capillary density in the peri-infarct zone were measured. Bone marrow-derived EPCs were isolated from mice to measure the proliferation, migration, and in vitro angiogenesis of EPCs after myocardial infarction exercise. The expression of NRG-1/ErbB4 signaling factor and related proteins in downstream PI3K/AKT signaling pathway were detected, and the level of autocrine NRG-1 in EPCs was detected. Post-MI resistance training, aerobic exercise training, and combined exercise training increased EPC mobilization and proliferation, migration, and tube-forming capacity, promoted myocardial vascular regeneration, improved cardiac function, and reduced infarct size. Exercise training upregulated NRG-1 expression in EPCs, and NRG-1/ErbB4 signaling activated the downstream PI3K/Akt signaling pathway. Moreover, EPCs may have a positive feedback autocrine loop with NRG-1 to improve the function of EPCs and promote vascular repair and regeneration in mice with MI. Exercise training after MI promotes the function of bone marrow-derived EPCs through NRG-1/ErbB4/PI3K/AKT signaling, thus exerting a role in angiogenesis.