Pulsed electromagnetic fields (PEMF) have been shown to accelerate proliferation and regeneration to the damaged tissue, but its mechanism remains unclear. Here, we examine whether PEMF therapy improves postnatal neovascularization using murine model of hindlimb ischemia, and investigate the underlying cellular/molecular mechanisms.Methods and Results
Hindlimb ischemia was induced by unilateral femoral artery resection using 6–8 week-old male C57BL6 mice. PEMF therapy (8 min/cycle, 30 ± 3 Hz, 5 mT) was then performed 4 cycles/day. At postoperative day 21, accelerated wound healing, decreased prevalence of gangrene and increased capillary density were observed among the PEMF-exposed mice. Moreover, the levels of vascular endothelial growth factor (VEGF) expression, endothelial nitric oxide synthase (eNOS) and Akt phosphorylation contained in the ischaemic muscles were increased in response to PEMF therapy. In vitro , PEMF interrupted the process of hypoxia-induced apoptosis and contributed to the tube-formative and proliferative capacities of human umbilical vein endothelial cells. PEMF exposure increased the level of VEGF in the conditioned media, as well as the eNOS and Akt phosphorylation in the cell lysate, and these PEMF-mediated angiogenic benefits could be blocked after PI3K inhibitor was administrated.Conclusions
In conclusion, Our data indicated that PEMF enhanced ischemia-mediated angiogenesis, through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway. Therefore, PEMF may be valuable for the treatment of the patients with critical limb ischemia.