Systemic inflammatory stimulation by microparticles derived from hypoxic trophoblast as a model for inflammatory response in preeclampsia

Lee, Seung Mi; Romero, Roberto; Lee, You Jeong; Park, In Sook; Park, Chan Wook; Yoon, Bo Hyun

doi:10.1016/j.ajog.2012.06.047

Cited by 49 publications

(53 citation statements)

References 43 publications

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“…Placental hypoxia, which is the main pathologic feature of PE, can cause trophoblast hypoxia, necrosis, and apoptosis (8,9). HMGB1 released actively or passively by hypoxia trophoblast increased the permeability of endothelial cell monolayer by TLR4-CAV-1 pathway.…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that HMGB1 increases endothelial cell permeability in sepsis and cerebral ischemic pathogenesis by activation of pattern recognition receptors, TLR4, TLR2, and the receptor for advanced glycation endproducts (RAGE) (11,12). High endothelial cell permeability is the main cause of general edema and high urine protein in PE (8); however, the underlying pathogenic relationship between HMGB1 and endothelial cell dysfunction in PE remains unexplored.…”

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confidence: 99%

“…Placental hypoxia can cause trophoblast necrosis and apoptosis (9). Postischemic inflammation is an essential step in the progression of endothelial cell injury in PE (8). A recent study showed that HMGB1 serum levels are increased in severe PE, most notably in patients experiencing early-onset PE (10).…”

mentioning

confidence: 99%

“…Preeclampsia (PE) is an oxidative stress process in the placenta leading to hypertension, proteinuria, edema, endothelial cell dysfunction, and placenta atherosclerosis (8). Placental hypoxia can cause trophoblast necrosis and apoptosis (9).…”

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confidence: 99%

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Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway

Jiang¹,

Cai

Zhu

et al. 2014

The Journal of Immunology

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High mobility group box 1 (HMGB1) plays an important role in the pathologic processes of endothelial permeability under oxidative stress. Trophoblast oxidative stress has been implicated in the pathophysiology of preeclampsia (PE). HMGB1 serum levels are increased in PE. However, the potential roles of HMGB1 in endothelial permeability in PE remain unclear. We assessed the effects of the hypoxic trophoblast on the permeability of the endothelial monolayer. Our results showed that the hypoxic trophoblast displayed higher HMGB1 mRNA, intracellular HMGB1 protein, and HMGB1 in conditioned medium than those of the normoxic trophoblast did. The hypoxic trophoblast conditioned medium increased the endothelial monolayer permeability and increased TLR 4 and caveolin-1 (CAV-1) protein expression in endothelial cells, which was inhibited by glycyrrhizic acid and HMGB1 small interfering RNA transfection to trophoblasts before hypoxia. The increased endothelial permeability induced by hypoxic trophoblast conditioned medium could be inhibited with TLR4 or CAV-1 gene silencing in endothelial cells. Immunoprecipitation showed that CAV-1 and TLR4 are colocalized in HUVECs and C57BL/6 mouse kidney. TLR4 small interfering RNA suppressed CAV-1 protein expression in endothelial cells upon stimulation of hypoxic trophoblast conditioned medium or HMGB1. We conclude that hypoxic trophoblasts play an important role in the mechanism of general edema (including protein urine) in PE via increasing endothelial monolayer permeability through the HMGB1/TLR4/CAV-1 pathway.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway

Jiang¹,

Cai

Zhu

et al. 2014

The Journal of Immunology

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“…73 In addition, in vitro research has indicated that PE-derived STBEVs differentially affect immune cells, endothelial cells, and platelet activation, suggesting a key role in maintenance of the MSIR. 74 STBEVs have been identified in maternal circulation in the first trimester of normal pregnancy and also found to be significantly elevated in early-onset PE. 75 Moreover, it is known that STBEVs contain subpopulations of EVs.…”

Section: Syncytiotrophoblast Extracellular Vesiclesmentioning

confidence: 99%

Placenta-derived exosomes: potential biomarkers of preeclampsia

Pillay¹,

Moodley²,

Moodley³

et al. 2017

IJN

111

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Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal–fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

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The diagnosis values of serum STAT4 and sEng in preeclampsia

Zhang¹,

Li²,

Zhou³

et al. 2019

Clinical Laboratory Analysis

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Objective To detect the levels of signal transducer and activator of transcription 4 (STAT4) and soluble endoglin (sEng) in preeclampsia patients and analyze the diagnostic values of STAT4 and sEng in preeclampsia. Methods Fifty‐four pregnant women with preeclampsia from October 2017 to June 2018 were included in this study. Twenty‐eight matched healthy pregnant women were set as the control group. The general clinical characteristics were measured. Serum STAT4 and sEng were detected by ELISA. Correlation between STAT4 and sEng, and their diagnostic value in preeclampsia were analyzed. Results Compared with control, the prothrombin time in preeclampsia was significantly lower, while the mean arterial pressure, 24‐hour urine protein, serum creatinine, fibrinogen, and ALT were significantly higher. The circulating levels of STAT4 and sEng were significantly increased in the preeclampsia. The serum levels of STAT4 and sEng in preeclampsia were positively correlated. For the diagnosis of preeclampsia by the serum STAT4, AUC is 0.902, and the sensitivity and specificity are 0.893 and 0.929. By the serum sEng, AUC is 0.873, and the sensitivity and specificity are 0.816 and 0.905. Conclusion The serum levels of STAT4 and sEng were significantly increased in preeclampsia with disease severity status, which have promise as diagnostic markers in preeclampsia.

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Systemic inflammatory stimulation by microparticles derived from hypoxic trophoblast as a model for inflammatory response in preeclampsia

Cited by 49 publications

References 43 publications

Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway

Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway

Placenta-derived exosomes: potential biomarkers of preeclampsia

The diagnosis values of serum STAT4 and sEng in preeclampsia

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