Gao Li, Qi Hong-Bo, Kamana K C, Zhang Xue-Mei, Zhang Hua, Baker Philip N
aDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University bCanada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, People's Republic of China cLiggins Institute, University of Auckland, Auckland, New Zealand.
J Hypertens. 2015 Jan;33(1):106-17. doi: 10.1097/HJH.0000000000000366.
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.
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.
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.
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.
子痫前期影响5% - 7%的正常妊娠，其特征为高血压和蛋白尿。尽管子痫前期的发病机制仍未完全明确，但螺旋动脉转化失败和胎盘血管异常被认为是该疾病的特征。研究还表明自噬活性增加。在本研究中，我们调查了氧化应激是否会增加自噬活性，进而影响滋养层细胞侵袭和胎盘血管系统。
采用18例合并子痫前期的妊娠胎盘、18例正常妊娠胎盘、滋养层HTR8/SVneo细胞系（HTR8/SVneo）的绒毛外滋养层细胞以及人脐静脉内皮细胞（HUVECs）。通过免疫组织化学、蛋白质印迹法和逆转录 - 聚合酶链反应（RT - PCR）对胎盘组织以及用氧化应激诱导剂葡萄糖氧化酶处理过的滋养层细胞和内皮细胞中的自噬标志物LC3、Beclin - 1和自噬体水平进行定量分析。在经葡萄糖氧化酶处理的HTR8/SVneo细胞或HUVECs中评估滋养层细胞侵袭和内皮细胞管形成情况。
早发型子痫前期妊娠胎盘以及用葡萄糖氧化酶处理过的HTR8/SVneo细胞和HUVECs中，LC3、Beclin - 1和自噬体的表达显著增加。此外，经葡萄糖氧化酶处理的HTR8/SVneo细胞或HUVECs中，滋养层细胞侵袭和内皮细胞管形成显著减少。
我们的数据表明，氧化应激诱导滋养层细胞或内皮细胞自噬增加，进而影响滋养层细胞侵袭和胎盘血管系统。过度的自噬活性可能参与子痫前期的发生发展。
