Chen Yihong, Ye Liyan, Guan Linbo, Fan Ping, Liu Rui, Liu Hao, Chen Jinxin, Zhu Yue, Wei Xing, Liu Yu, Bai Huai
Laboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
Biol Open. 2018 Sep 19;7(9):bio035204. doi: 10.1242/bio.035204.
Electrical stimulation induces significant neovessel formation We have shown that electrical stimulation of endothelial cells functions as an important contributor to angiogenesis in monolayer culture. Because angiogenesis occurs in a three-dimensional (3D) environment, in this study we investigated the effects of a direct current (DC) electrical field (EF) on endothelial neovessel formation in 3D culture. There was a significant increase in tube formation when endothelial cells were stimulated with EF for 4 h. The lengths of the tube-like structures were augmented further by the continued EF exposure. The lengths of the tubes also increased dose-dependently in the EF-treated cultures in the field strengths of 50 mV/mm∼200 mV/mm for 6 h. Electrical fields of small physiological magnitude enhanced VEGF expression by endothelial cells in 3D culture. EF treatment also resulted in activation of VEGFR2, Akt, extracellular regulated kinase 1,2 (Erk1/2), as well as the c-Jun NH2-terminal kinase (JNK). The tyrosine kinase inhibitor SU1498 that blocks VEGFR2 activity exhibited a potent inhibition of tube growth, and the Akt inhibitor MK-2206 2HCl, the Erk1/2 inhibitor U0126 and the JNK inhibitor SB203580 significantly reduced EF-stimulated tubulogenesis. These results suggest the importance of the VEGFR2 signaling pathway during EF-induced angiogenesis. The results of this study provide novel evidence that endogenous EFs may promote blood vessel formation of endothelial cells by activating the VEGF receptor signaling pathway.
电刺激可诱导显著的新血管形成 我们已经表明，在单层培养中，对内皮细胞进行电刺激是血管生成的一个重要促成因素。由于血管生成发生在三维（3D）环境中，在本研究中，我们研究了直流（DC）电场（EF）对3D培养中内皮新血管形成的影响。当用EF刺激内皮细胞4小时时，管形成显著增加。通过持续暴露于EF，管状结构的长度进一步增加。在50 mV/mm至200 mV/mm的场强下，对EF处理的培养物进行6小时处理，管的长度也呈剂量依赖性增加。小生理强度的电场增强了3D培养中内皮细胞的VEGF表达。EF处理还导致VEGFR2、Akt、细胞外调节激酶1,2（Erk1/2）以及c-Jun NH2末端激酶（JNK）的激活。阻断VEGFR2活性的酪氨酸激酶抑制剂SU1498对管生长表现出强烈的抑制作用，Akt抑制剂MK-2206 2HCl、Erk1/2抑制剂U0126和JNK抑制剂SB203580显著降低了EF刺激的管状形成。这些结果表明VEGFR2信号通路在EF诱导的血管生成过程中的重要性。本研究结果提供了新的证据，即内源性EFs可能通过激活VEGF受体信号通路促进内皮细胞的血管形成。
