Abstract
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.
Highlights
Preeclampsia (PE) is defined as hypertension with a blood pressure (BP) ≥ 140/90 mmHg and substantial proteinuria that is ≥300 mg in 24 h at or after 20 weeks of gestation
Blood pressure values and proteinuria were significantly higher in women who experienced EOPE than in normal women
Numerous theories have been proposed to explain the occurrence of preeclampsia, and it is widely accepted that impaired angiogenesis and trophoblast apoptosis at the maternal–fetal interface play roles (Kasture et al, 2018; Raguema et al, 2020)
Summary
Preeclampsia (PE) is defined as hypertension with a blood pressure (BP) ≥ 140/90 mmHg and substantial proteinuria that is ≥300 mg in 24 h at or after 20 weeks of gestation. Preeclampsia is considered to be of placental origin and is associated with increased oxidative stress, which could disturb angiogenesis and lead cell apoptosis. Trophoblast cells proliferate and differentiate through two potential pathways described as villous and extravillous: villous cytotrophoblast cells fuse into the multinucleated syncytiotrophoblast, which forms the outer epithelial layer of the chorionic villi and extravillous trophoblast (EVT) cells migrate into the decidua and remodel uterine arteries (Gude et al, 2004) The impaired invasion of EVT cells into uterine spiral arteries could influence angiogenesis in the placenta and disturb the maternal myometrial spiral artery remodeling, promote FLT1 releasing, and induce maternal intravascular systemic inflammatory response and endothelial dysfunction (Steegers et al, 2010). The state of inflammation can further activate and promote the programmed death of trophoblasts, a process called apoptosis (Raguema et al, 2020). The activation of apoptosis can backfire on the trophoblasts, significantly disrupting cell migration and placental vascularization, while exacerbating immune responses (Sharp et al, 2010)
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