Wang W, Merrill M J, Borchardt R T
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047, USA.
Am J Physiol. 1996 Dec;271(6 Pt 1):C1973-80. doi: 10.1152/ajpcell.1996.271.6.C1973.
Vascular endothelial growth factor (VEGF), which stimulates endothelial cell growth and induces hyperpermeability of the microvasculature, plays an important role in normal and tumor-vasculature development and tumor edema generation. In this study, we investigated the effect of VEGF on the permeability of cultured bovine brain microvessel endothelial cells (BMECs), an in vitro blood-brain barrier (BBB) model. We found that addition of purified VEGF to both the apical and basolateral sides of the BMEC monolayers increased the permeability of the monolayer to [14C]sucrose (approximately 3-fold). A more significant increase in permeability was observed when VEGF was applied to the basolateral side of the monolayer (3-fold) than to the apical side (1.5-fold). The permeability-increasing activity of VEGF on the BMEC monolayers is both dose and time dependent. The VEGF-induced permeability increase in BMECs requires a long incubation time with VEGF, and the effect is durable. These results suggest that this cell culture system may be useful for exploring the role of VEGF in regulating the permeability of the BBB, for studying the mechanism of the permeability-increasing effect of VEGF on the endothelial cells, and for evaluating the strategies to regulate the activity of VEGF.
血管内皮生长因子（VEGF）可刺激内皮细胞生长并诱导微血管的高通透性，在正常和肿瘤血管生成以及肿瘤水肿形成过程中发挥重要作用。在本研究中，我们调查了VEGF对培养的牛脑微血管内皮细胞（BMECs）通透性的影响，BMECs是一种体外血脑屏障（BBB）模型。我们发现，在BMEC单层细胞的顶侧和基底外侧均添加纯化的VEGF，会增加单层细胞对[14C]蔗糖的通透性（约3倍）。当将VEGF应用于单层细胞的基底外侧时（3倍），观察到的通透性增加比应用于顶侧时（1.5倍）更为显著。VEGF对BMEC单层细胞的通透性增加活性具有剂量和时间依赖性。VEGF诱导的BMECs通透性增加需要与VEGF长时间孵育，且该效应持久。这些结果表明，这种细胞培养系统可能有助于探索VEGF在调节血脑屏障通透性中的作用，研究VEGF对内皮细胞通透性增加作用的机制，以及评估调节VEGF活性的策略。
