Cunha Filipa, Rajnicek Ann M, McCaig Colin D
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom,
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
J Vasc Res. 2019;56(1):39-53. doi: 10.1159/000495311. Epub 2019 Apr 17.
Natural direct current electric fields (DC EFs) within tissues undergoing angiogenesis have the potential to influence vessel formation, but how they affect endothelial cells is not clear. We therefore quantified behaviours of human umbilical vein endothelial cells (HUVEC) and human microvasculature endothelial cells (HMEC) stimulated by EFsin vitro. Both cell types migrated faster and toward the cathode; HUVECs responded to fields as low as 50mV/mm, but the HMEC threshold was 100 mV/mm. Mitosis was stimulated at 50 mV/mm for HMEC and at 150 mV/mm for HUVECs, but the cleavage plane was oriented orthogonal to the field vector at 200 mV/mm for both cell types. That different field strengths induced different cell responses suggests distinct underlying cellular mechanisms. A physiological electric field also upregulated expression of CXCR4 and CXCR2 chemokine receptors and upregulated phosphorylation of both chemokines in HUVEC and HMEC cells. Evidence that DC EFs direct endothelial cell migration, proliferation and upregulate chemokines involved in wound healing suggests a key role for electrical control of capillary production during healing. Our data contribute to the molecular mechanisms by which DC EFs direct endothelial cell behaviour and present a novel signalling paradigm in wound healing, tissue regeneration and angiogenesis-related diseases.
处于血管生成过程中的组织内的自然直流电场（DC EFs）有可能影响血管形成，但它们如何影响内皮细胞尚不清楚。因此，我们在体外对受电场刺激的人脐静脉内皮细胞（HUVEC）和人微血管内皮细胞（HMEC）的行为进行了量化。两种细胞类型均迁移得更快且朝着阴极迁移；HUVECs对低至50mV/mm的电场有反应，但HMEC的阈值为100 mV/mm。对于HMEC，在50 mV/mm时刺激有丝分裂，对于HUVECs，在150 mV/mm时刺激有丝分裂，但对于两种细胞类型，在200 mV/mm时分裂平面与场向量正交。不同的场强诱导不同的细胞反应，这表明存在不同的潜在细胞机制。生理电场还上调了HUVEC和HMEC细胞中CXCR4和CXCR2趋化因子受体的表达，并上调了两种趋化因子的磷酸化。直流电场指导内皮细胞迁移、增殖并上调参与伤口愈合的趋化因子，这一证据表明在愈合过程中电控制毛细血管生成具有关键作用。我们的数据有助于揭示直流电场指导内皮细胞行为的分子机制，并在伤口愈合、组织再生和血管生成相关疾病中呈现一种新的信号传导模式。
