Hypoxic trophoblast‐derived sFlt‐1 may contribute to endothelial dysfunction: implication for the mechanism of trophoblast—endothelial dysfunction in preeclampsia
Hypoxic trophoblast‐derived sFlt‐1 may contribute to endothelial dysfunction: implication for the mechanism of trophoblast—endothelial dysfunction in preeclampsia
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DOI：
10.1042/cbi20100020
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发表时间：
2010-09
影响因子：
3.9
通讯作者：
Qiong Zhou;F. Qiao;Chang Zhao;Haiyi Liu
中科院分区：
文献类型：
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作者：
Qiong Zhou;F. Qiao;Chang Zhao;Haiyi Liu
广泛的内皮功能障碍的母体系统性疾病是了解先兆子痫发展的主要焦点。sFlt-1（可溶性fms样酪氨酸激酶受体1）是血管内皮生长因子（vascular endothelial growth factor，VEGF）的内源性抑制剂，在内皮功能障碍中可能发挥重要作用。本研究旨在通过建立缺氧的TEV-1 s（人早孕绒毛外滋养层细胞）和HUVEC（人脐静脉内皮细胞）共培养模型来确定缺氧滋养层细胞来源的sFlt-1是否会导致内皮功能障碍。结果表明，与HUVECs相比，低氧处理以时间依赖的方式显著促进TEV-1 s中sFlt-1 mRNA和蛋白的表达。当HUVECs与缺氧的TEV-1共培养时，内皮功能（以HUVECs的NO（一氧化氮）合成和单层屏障功能为特征）显著降低，伴随着细胞条件培养基中sFlt-1的增加和VEGF的减少。此外，上述观察到的内皮功能障碍与VEGF siRNA处理的培养物中观察到的功能障碍一致。本文所述的结果表明，长期缺氧的滋养层细胞可能释放足够的sFlt-1，通过剥夺细胞的VEGF活性导致内皮功能障碍。
The maternal systemic disorder of widespread endothelial dysfunction is a primary focus in understanding the development of preeclampsia. sFlt‐1 (soluble fms‐like tyrosine kinase receptor 1), an endogenous inhibitor of VEGF (vascular endothelial growth factor), may play important roles in endothelial dysfunction. The present study aimed to determine whether hypoxic trophoblast‐derived sFlt‐1 could lead to endothelial dysfunction by establishing a cocultured model of anoxic TEV‐1s (human first‐trimester extravillous trophoblasts) and HUVECs (human umbilical vein endothelial cells). The results showed that the hypoxic treatment significantly promoted sFlt‐1 mRNA and protein expression in TEV‐1s in a time‐dependent manner compared with the effect in HUVECs. When HUVECs were cocultured with anoxic TEV‐1s, the endothelial function, which was characterized by NO (nitric oxide) synthesis and monolayer barrier function of HUVECs, were notably decreased, accompanied by increasing sFlt‐1 and decreasing VEGF in cell‐conditioned medium. Moreover, the observed endothelial dysfunction described above was consistent with the dysfunction observed in VEGF siRNA‐treated cultures. The findings presented herein imply that chronically hypoxic trophoblasts may release sufficient sFlt‐1 to cause endothelial dysfunction by depriving cells of VEGF activity.