title: Pulsed electromagnetic field improves postnatal neovascularization in response to hindlimb ischemia.
abstract: Pulsed electromagnetic fields (PEMF) have been shown to promote proliferation and regeneration in the damaged tissue. Here, we examined whether PEMF therapy improved postnatal neovascularization using murine model of hindlimb ischemia, and the underlying cellular/molecular mechanisms were further investigated. Hindlimb ischemia was induced by unilateral femoral artery resection using 6-8 week-old male C57BL6 mice. Then, mice were exposed to extracorporeal PEMF therapy (4 cycles, 8min/cycle, 30 ± 3 Hz, 5 mT) every day until day 14. Our data demonstrated that PEMF therapy significantly accelerated wound healing, decreased prevalence of gangrene and increased postnatal neovascularization. Moreover, the levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and Akt phosphorylation in ischemic muscles were markedly enhanced following PEMF therapy. In vitro, PEMF inhibited the process of hypoxia-induced apoptosis and augmented tube formation, migration and proliferative capacities of human umbilical vein endothelial cells (HUVECs). Additionally, PEMF exposure increased VEGF secretion, as well as the eNOS and Akt phosphorylation, and these benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. In conclusion, our data indicated that PEMF therapy enhanced ischemia-mediated angiogenesis, through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway. Therefore, PEMF should be a valuable treatment for the patients with critical limb ischemia.
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Li
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Jing-Juan
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
authors.forename: Yi-Qin
authors.initials: YQ
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology, Gong li Hospital Miaopu Road 219, Shanghai 200135, China.
authors.forename: An
authors.initials: A
authors.lastname: Hu
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Lu
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Shen-Qi
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Han
authors.affiliation: Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
authors.forename: Chang-Ning
authors.initials: CN
authors.lastname: Hao
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Duan
keywords: Pulsed electromagnetic fields (PEMF); VEGF; angiogenesis; eNOS; hindlimb ischemia