Syncytiotrophoblast-Derived Extracellular Vesicles in Pathophysiology of Preeclampsia

Han, Choong‐Hee; Han, Lulu; Huang, Pengzhu; Chen, Yuanyuan; Wang, Yingmei; Xue, Fengxia

doi:10.3389/fphys.2019.01236

Cited by 37 publications

(37 citation statements)

References 87 publications

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“…These EVs, upon binding, induce a shift in the cytokine secretion profile of the neighboring cells, causing the release of anti-inflammatory cytokines (64). On the other hand, in preeclampsia when placental ischemia and hypoxia are present, a greater number of the STB cells undergo apoptosis (68). There is subsequently an increase in secreted EVs into the maternal circulation, overwhelming the body's ability to adequately scavenge and clear them effectively (68,69).…”

Section: Syncytiotrophoblast Cells and Their Secreted Extracellular Vmentioning

confidence: 99%

“…On the other hand, in preeclampsia when placental ischemia and hypoxia are present, a greater number of the STB cells undergo apoptosis ( 68 ). There is subsequently an increase in secreted EVs into the maternal circulation, overwhelming the body's ability to adequately scavenge and clear them effectively ( 68 , 69 ). These vesicles then act as antigenic stimuli for components of the immune system leading to unintended endothelial injury, inflammation, and hyper-coagulation ( 68 ).…”

Section: Syncytiotrophoblast Cells and Their Secreted Extracellular Vmentioning

confidence: 99%

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Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

et al. 2020

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Section: Syncytiotrophoblast Cells and Their Secreted Extracellular Vmentioning

confidence: 99%

Section: Syncytiotrophoblast Cells and Their Secreted Extracellular Vmentioning

confidence: 99%

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

et al. 2020

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“…In mouse models, we further showed that these pcEVs induce hypertension and proteinuria not only in pregnant mice but also in non-pregnant mice [ 21 ], demonstrating the importance of pcEVs in the pathogenesis of PE. These pcEVs can cause PE through multiple pathways [ 48 ] by (1) promoting coagulation through PS exposed on their surfaces [ 21 , 22 , 49 ], (2) expressing tissue factor to trigger extrinsic coagulation [ 49 ], and (3) activating platelets and endothelial cells to release procoagulant extracellular vesicles [ 21 ]. Together, these findings demonstrate that PE is initiated by placental factors and propagated by maternal factors in the systemic proinflammatory and hypercoagulable states, which are closely associated with oxidative stress.…”

Section: The Pe-associated Hypercoagulable Statementioning

confidence: 99%

Oxidative Stress and Preeclampsia-Associated Prothrombotic State

et al. 2020

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Preeclampsia (PE) is a common obstetric disease characterized by hypertension, proteinuria, and multi-system dysfunction. It endangers both maternal and fetal health. Although hemostasis is critical for preventing bleeding complications during pregnancy, delivery, and post-partum, PE patients often develop a severe prothrombotic state, potentially resulting in life-threatening thrombosis and thromboembolism. The cause of this thrombotic complication is multi-factorial, involving endothelial cells, platelets, adhesive ligands, coagulation, and fibrinolysis. Increasing evidence has shown that hemostatic cells and factors undergo oxidative modifications during the systemic inflammation found in PE patients. However, it is largely unknown how these oxidative modifications of hemostasis contribute to development of the PE-associated prothrombotic state. This knowledge gap has significantly hindered the development of predictive markers, preventive measures, and therapeutic agents to protect women during pregnancy. Here we summarize reports in the literature regarding the effects of oxidative stress and antioxidants on systemic hemostasis, with emphasis on the condition of PE.

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“…PE is a pregnancy-related hypertensive disorder characterized by an insufficient trophoblast invasion into the maternal spiral arteries, deregulated proliferation and enhanced apoptosis ( 5 , 6 ). PE is also a major contributor to perinatal morbidity and mortality ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

Duan

Schimmelmann

et al. 2020

Front. Endocrinol.

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Objectives An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis which are all crucial to establishing a successful pregnancy. Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta (AIP) disorders ( Placenta accreta , increta , or percreta) which are characterized by excessive trophoblast invasion. Both of them will cause maternal and fetal morbidity/mortality. However, the etiology of these diseases is still unclear. Our previous study has shown that the matricellular protein nephroblastoma overexpressed (NOV, CCN3) induces G0/G1 cell cycle arrest, drives trophoblast cells into senescence and activates FAK and Akt kinases resulting in reduced cell proliferation and enhanced migration capability of the human trophoblast cell line SGHPL-5. The present study focuses on whether CCN3 can alter cell cycle-regulated pathways associated with trophoblast senescence and invasion activity in pathological versus gestational age-matched control placentas. Methods Cell cycle regulator proteins were investigated by immunoblotting and qPCR. For localization of CCN3, p16, p21, and Cyclin D1 proteins, co-immunohistochemistry was performed. Results In early-onset PE placentas, CCN3 was expressed at a significantly lower level compared to gestational age-matched controls. The decrease of CCN3 level is associated with an increase in p53, Cyclin E1 and pRb protein expression, whereas the level of cleaved Notch-1, p21, Cyclin D1, pFAK, pAKT, and pmTOR protein decreased. In term AIP placentas, the expression of CCN3 was significantly increased compared to matched term controls. This increase was correlated to an increase in p53, p16, p21, Cyclin D1, cleaved Notch-1, pFAK, pAkt, and pmTOR whereas pRb was significantly decreased. However, in late PE and early AIP placentas, no significant differences in CCN3, p16, p21, Cyclin D1, p53, and cleaved Notch-1 expression were found when matched to appropriate controls. Conclusions CCN3 expression levels are correlated to markers of cell cycle arrest oppositely in PE and AIP by activating the FAK/AKT pathway in AIP or down-regulating in PE. This may be one mechanism to explain the different pathological features of placental diseases, PE and AIP.

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Syncytiotrophoblast-Derived Extracellular Vesicles in Pathophysiology of Preeclampsia

Cited by 37 publications

References 87 publications

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

Oxidative Stress and Preeclampsia-Associated Prothrombotic State

CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

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