DataSheet3_Autophagy Activation by Hypoxia Regulates Angiogenesis and Apoptosis in Oxidized Low-Density Lipoprotein-Induced Preeclampsia.PDF

Objective: Autophagy influences a wide range of physiological and pathological processes in the human body. In this study, we aimed to investigate the role of autophagy in early-onset preeclampsia (EOPE); autophagy activation by hypoxia could rescue impaired angiogenesis and apoptosis in preeclampsia, leading by ox-LDL.
Methods: Transmission electron microscopy was applied to identify autolysosomes in trophoblast cells of the placenta apical region. Quantitative real-time polymerase chain reaction, Western blot, flow cytometry, and wound-healing assays were adopted to determine autophagy activity, angiogenesis, and apoptosis in placenta tissues or HTR8/SVneo cells.
Results: Autophagy activity was inhibited in the placenta of women who experienced EOPE; autophagy activation by hypoxia enhanced the migration ability, rescued ox-LDL–mediated impaired angiogenesis in HTR8/SVneo cells [vascular endothelial growth factor A (VEGFA) downregulation and FMS-like tyrosine kinase-1 (FLT1) upregulation], and protected against cell apoptosis (BAX downregulation).
Conclusion: Autophagy could maintain the function of trophoblast cells by differentially regulating the expression of VEGFA and FLT1 and protecting against cell apoptosis at the maternal–fetal interface, potentially related to prevention of preeclampsia.

研究目的：自噬（autophagy）广泛参与人体诸多生理与病理过程。本研究旨在探讨自噬在早发型子痫前期（early-onset preeclampsia, EOPE）中的作用；缺氧（hypoxia）介导的自噬激活可改善氧化低密度脂蛋白（ox-LDL）诱导的子痫前期中受损的血管生成（angiogenesis）与细胞凋亡（apoptosis）。
研究方法：采用透射电子显微镜（Transmission electron microscopy）观察胎盘顶区滋养层细胞（trophoblast cells）内的自噬溶酶体（autolysosomes）；通过实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction）、蛋白质印迹法（Western blot）、流式细胞术（flow cytometry）及划痕愈合实验（wound-healing assays），检测胎盘组织或HTR8/SVneo细胞的自噬活性、血管生成能力与细胞凋亡水平。
研究结果：早发型子痫前期患者胎盘组织中的自噬活性受到抑制；缺氧介导的自噬激活可增强HTR8/SVneo细胞的迁移能力，改善ox-LDL诱导的受损血管生成（表现为血管内皮生长因子A（vascular endothelial growth factor A, VEGFA）下调与Fms样酪氨酸激酶1（FMS-like tyrosine kinase-1, FLT1）上调），并抑制细胞凋亡（表现为Bcl-2相关X蛋白（BAX）下调）。
研究结论：自噬可通过差异性调控血管内皮生长因子A（VEGFA）与Fms样酪氨酸激酶1（FLT1）的表达，并在母胎界面抑制细胞凋亡，从而维持滋养层细胞功能，或与子痫前期的防治存在潜在关联。