Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia
Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia
复制标题
过度自噬导致滋养层侵袭和脉管系统失败：可能与先兆子痫的发病机制有关。
DOI：
10.1097/hjh.0000000000000366
复制
发表时间：
2015-01-01
影响因子：
4.9
通讯作者：
Baker, Philip N.
中科院分区：
文献类型：
--
作者：
Gao, Li;Qi, Hong-Bo;Baker, Philip N.
前言：子痫前期影响5-7%的健康孕妇，以高血压和蛋白尿为特征。尽管先兆子痫的发病机制尚不完全清楚，但螺旋动脉转化失败和胎盘血管异常被认为是该病的一个方面。研究还表明，自噬活性增加。方法：取18例子痫前期患者和18例正常妊娠患者的胎盘、滋养细胞HTR8/SVneo细胞系(HTR8/SVneo)、绒毛外滋养层细胞和人脐静脉内皮细胞。用免疫组织化学、Western blotting和RT-PCR方法检测胎盘组织、经氧化应激诱导剂葡萄糖氧化酶处理的滋养层细胞和内皮细胞中自噬标志物LC3、Beclin-1和自噬小体的表达水平。结果：早发性子痫前期患者胎盘组织及经葡萄糖氧化酶处理的HTR8/SVneo细胞和HUVECs中，胎盘组织中Lc3、Beclin-1和自噬小体的表达均显著增加。此外，经葡萄糖氧化处理的HTR8/SVneo细胞或HUVECs的滋养层细胞侵袭和内皮细胞管形成明显减少。结论：氧化应激诱导滋养层细胞或内皮细胞自噬增加，从而影响滋养层细胞侵袭和胎盘血管形成。过度的自噬活动可能参与了子痫前期的发展。
Introduction: Preeclampsia affects 5-7% of all healthy pregnancies and is characterized by hypertension and proteinuria. Although the pathogenesis of preeclampsia is still not fully understood, a failure of spiral artery transformation and aberrant placental vasculature are considered to be facets of this disease. Studies have also implicated increased autophagic activity. In this study, we investigated whether oxidative stress could increase autophagic activity and consequently affect trophoblast invasion and the placental vasculature.Methods: Placentas from 18 pregnancies complicated by preeclampsia and from 18 uncomplicated pregnancies, trophoblast HTR8/SVneo cell line (HTR8/SVneo) extravillous trophoblasts, and human umbilical vein endothelial cells (HUVECs) were employed. The levels of autophagy markers LC3, Beclin-1 and autophagosome were quantified by immunohistochemistry, Western blotting and RT-PCR in placental tissue, and in trophoblasts and endothelial cells that had been treated with an oxidative stress inducer glucose oxidase. Trophoblast invasion and endothelial cell tube formation were assessed in HTR8/SVneo cells or HUVECs that had been treated with glucose oxidase.Results: The expression of LC3, Beclin-1 and autophagosome was significantly increased in placentas from pregnancies complicated by early-onset preeclampsia and in HTR8/SVneo cells and HUVECs treated with glucose oxidase. In addition, trophoblast invasion and endothelial cell tube formation were significantly reduced in HTR8/SVneo cells or HUVECs that had been treated with glucose oxidase.Conclusion: Our data suggest that oxidative stress induces increased autophagy in trophoblasts or endothelial cells which affects trophoblast invasion and the placental vasculature. Excessive autophagic activity may be involved in the development of preeclampsia.