Progression Of Preeclampsia Research Articles

Retracted: The Imbalance Expression of DLX3 May Perform Critical Function in the Occurrence and Progression of Preeclampsia

Retracted: The Imbalance Expression of DLX3 May Perform Critical Function in the Occurrence and Progression of Preeclampsia

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia.

The sirtuin regulator 1-related enzyme (SIRT1) has been shown to play an important role in various pathophysiological processes. Our aim was to investigate the effect and correlation of serum SIRT1 combined with uterine hemodynamic parameters on disease severity and fetal uterine growth restriction in the progression of preeclampsia and to evaluate its clinical value as a potential marker. A total of 100 patients with preeclampsia who were hospitalized in Qufu Normal University Hospital from June 2017 to June 2021 were selected as the research objects. According to the severity, they were divided into the mild (62 cases) and severe groups (38 cases), and according to whether the fetal growth restriction was combined or not, they were divided into the combined fetal growth restriction group (56 cases) and the uncomplicated fetal growth restriction group (44 cases). Serum SIRT1 expression and uterine artery hemodynamic parameters were detected, and Spearman analysis was used to evaluate the association of serum SIRT1 expression and uterine artery hemodynamic parameters (the peak-to-trough ratio of arterial blood velocity, the pulsatility index, and the resistance index) with disease severity (systolic blood pressure, diastolic blood pressure, and random urinary protein levels) and fetal growth restriction (femoral length, biparietal diameter, head circumference, and neonatal weight); unsupervised principal component analysis (PCA), supervised partial least-squares discrimination analysis (PLS-DA), cluster heat map analysis, the receiver operating characteristic (ROC) curve, and the area under curve (AUC) were used to evaluate the diagnostic value of serum SIRT1 expression combined with uterine artery hemodynamic parameters in the severity of disease and fetal growth restriction in patients with preeclampsia. Compared with patients with mild preeclampsia, serum SIRT1 expression was lower in patients with severe preeclampsia (p < 0.0001), the arterial blood flow velocity peak-to-trough ratio, pulsatility index, and resistance index were higher (p < 0.001; p < 0.0001); and serum SIRT1 expression and uterine artery hemodynamic parameters were closely related to disease severity (p < 0.001; p < 0.0001). In addition, the expression of serum SIRT1 in patients with preeclampsia combined with fetal growth restriction was lower than patients without preeclampsia (p < 0.0001); the peak-to-trough ratio of arterial blood flow velocity, the pulsatility index, and the resistance index were higher (p < 0.0001); and serum SIRT1 expression and uterine artery hemodynamics were closely related to fetal growth restriction (p < 0.0001). Unsupervised PCA analysis and supervised PLS-DA analysis showed that patients with different severity of disease and patients with or without fetal growth restriction were similar within the groups, and there were significant differences between the groups; cluster heat map analysis showed that the mild and severe groups were stratified clustering, and the combined fetal growth restriction group and the uncombined group were hierarchically clustered; ROC curve showed that the AUC of serum SIRT1 expression combined with uterine artery hemodynamic parameters was 0.776 in identifying the severity of preeclampsia and 0.956 in identifying the preeclampsia complicated by fetal growth restriction. Serum SIRT1 combined with uterine hemodynamic parameters in preeclampsia is closely related to disease severity and fetal growth restriction and is expected to become a potential biomarker for early clinical intervention in patients.

The Upregulated Exosome Protein ET-1 Induces the Increased Level of Ang-II and Contributes to the Progression of Pre-Eclampsia

The Upregulated Exosome Protein ET-1 Induces the Increased Level of Ang-II and Contributes to the Progression of Pre-Eclampsia

SARS-COV-2 – НОВЫЙ ФАКТОР РИСКА РАЗВИТИЯ ПРЕЭКЛАМПСИИ

The study aims to assess the risks for preeclampsia progression in pregnant women with SARS-CoV-2 based on the study obtained in 2021, which included the pregnancy course and outcome of 1 122 women divided into three groups. The groups were as following: 52 pregnant women with positive SARS-CoV-2 and preeclampsia, 302 women with negative SARS-CoV-2 and preeclampsia, and 768 pregnant women with positive SARS-CoV-2 and without preeclampsia. Chronic arterial hypertension prevailed in women with positive SARS-CoV-2 and preeclampsia by 2.5 times in comparison with those with negative SARS-CoV-2 and preeclampsia, and by 10.4 times in comparison with those with positive SARS-CoV-2 and without preeclampsia. Assisted reproductive technologies were used for pregnant women with positive SARS-CoV-2 and preeclampsia 7.9 and 11.8 times more frequently than for other groups of women. Women with preeclampsia suffered from premature birth, premature detachment of the placenta, cesarean delivery, and asphyxia of newborns at a higher rate.

Fibrinogen beta chain may be a potential predict biomarker for pre-eclampsia: A preliminary study

ObjectiveThere are no approaches for the early detection of pre-eclampsia (PE). Using parallel reaction monitoring proteomics, we investigated 79 maternal serum protein changes before PE onset and its predictive capability. MethodsWe conducted a nested case-control study with 60 PE patients and 60 normotensive pregnant women matched for age and gestational week. These differentially expressed proteins were quantified using the data-dependent acquisition (DDA) combined parallel response monitoring (PRM) approach, and a PE prediction model was developed using the least absolute shrinkage and selection operator (LASSO) regression. We further examined the link between these biomarkers and PE using bioinformatics. ELISA assay was used to investigate the expression and clinical significance of the critical variables. ResultsAmong the 79 analyzed proteins, we identified 11 serum proteins with significantly abnormal expression. Fibrinogen beta chain (FGB) was likely connected with the progression of PE due to the positive correlation between their levels and those of hypertension and proteinuria. In addition, an early prediction model for PE with an AUC of 92% was developed using LASSO regression. ConclusionOur research employs predictive algorithms and screens for relevant variables, which could result in a potential approach to enhancing PE prediction.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

Circ_0004904 suppresses trophoblast cell proliferation, invasion and migration in preeclampsia via upregulating the expression of DNA damage inducible alpha by interacting with miR-19a-3p

ABSTRACT Preeclampsia (PE) is the most common complication in the pregnancy of women. PE progression was found to be associated with dysregulated circular RNAs (circRNAs), and we aimed to explore the pathological mechanism with circ_0004904 in PE. The circ_0004904, microRNA-19a-3p (miR-19a-3p) and DNA damage inducible alpha (GADD45A) were quantified via reverse transcription-quantitative polymerase chain reaction assay. Trophoblast cell behaviors were examined by cell viability using Cell Counting Kit-8 assay, cell proliferation using EdU assay, cell apoptosis using flow cytometry, cell invasion using transwell assay and migration using wound healing assay. Western blot was used for protein analysis of epithelial mesenchymal transition (EMT) and GADD45A. Dual-luciferase reporter assay and RNA immunoprecipitation assay were used for target interaction analysis. The circ_0004904 upregulation was detected in placenta tissues from PE patients. Trophoblast cell proliferation, invasion, migration and EMT were repressed but cell apoptosis was promoted after overexpression of circ_0004904. Circ_0004904 acted as a miR-19a-3p sponge in trophoblast cells, and all regulatory effects of circ_0004904 on trophoblast cell behaviors were reversed by miR-19a-3p upregulation. The miR-19a-3p directly targeted GADD45A and miR-19a-3p downregulation inhibited trophoblast cell development through elevating the GADD45A level. Moreover, circ_0004904 enhanced the expression of GADD45A via sponging miR-19a-3p. Our results elucidated that circ_0004904 reduced proliferation and cell motility of trophoblast cells via the miR-19a-3p-mediated GADD45A level elevation, indicating the involvement of circ_0004904/miR-19a-3p/GADD45A in PE progression.

Pre-Existing Diabetes Mellitus, Hypertension and KidneyDisease as Risk Factors of Pre-Eclampsia: A Disease of Theories and Its Association with Genetic Polymorphism.

Pre-existing diabetes, hypertension and kidney disorders are prominent risk factors of pre-eclampsia (PE). It is a multifactorial pregnancy disorder associated with high blood pressure, proteinuria, and multiorgan failure, which develops after the 20th week of pregnancy. It is one of the most feared pregnancy disorders, as it consumes thousands of fetomaternal lives per annum. According to clinical and pathological studies, the placenta appears to be a key player in the pathogenesis of PE; however, the exact origin of this disorder is still under debate. Defective placentation and angiogenesis are the hallmarks of PE progression. This angiogenic imbalance, together with maternal susceptibility, might determine the severity and clinical presentation of PE. This article comprehensively examines the mechanisms of pathogenesis of PE and current evidence of the factors involved in its progression. Finally, this article will explore the genetic association of PE, various candidate genes, their proposed mechanisms and variants involved in its pathogenesis.

Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis.

This study aimed to determine the role of long noncoding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in the occurrence and progression of preeclampsia (PE) and to determine the underlying molecular mechanisms. The associations between WT1-AS and microRNA (miR)-186-5p, and miR-186-5p and cell adhesion molecule 2 (CADM2) were predicted using StarBase software and verified via dual-luciferase assays. To explore the role of the human chorionic trophoblast line HTR-8/SVneo, gene (WT1-AS/miR-186-5p) gain/loss of function experiments were performed. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to evaluate transfection efficiency. Cell proliferation, apoptosis, cell migration, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell analysis, respectively. Moreover, CADM2 protein expression was measured by western blotting. The results indicated that overexpression of WT1-AS inhibited cell viability, migration, and invasion, and induced apoptosis in HTR-8/SVneo cells. We observed that miR-186a-5p directly targeted WT1-AS, and miR-186a-5p knockdown reversed the effects of WT1-AS knockdown in HTR-8/SVneo cells. Binding sites were found between miR-186-5p and CADM2, and CADM2-overexpression reversed the influence of miR-186-5p mimic on HTR-8/SVneo cells. In summary, our findings demonstrated that lncRNA WT1-AS participates in PE by regulating the proliferation and invasion of placental trophoblasts, through the miR-186-5p/CADM2 axis.

CircSTAM inhibits migration and invasion of trophoblast cells by regulating miR-148a-5p/PTEN axis

BackgroundThe mechanisms underlying the pathogenesis of preeclampsia (PE) remains unclear. Exploring the molecular players in PE progression can provide insights into targeted therapy.MethodsThe expression levels of circSTAM in placental chorionic tissues of PE patients and normal pregnant women were compared by RT-qPCR. CircSTAM was knocked down by small interfering RNA to investigate its role in migration, invasion and epithelial-mesenchymal transformation (EMT) of trophoblast HTR-8/SVneo cells. The downstream target of circSTAM was predicted using online bioinformatics resources, and their molecular interaction was examined by luciferase reporter assay.ResultsCircSTAM was upregulated in PE placenta tissues in comparison to normal placental tissues. CircSTAM knockdown significantly enhanced cellular invasion, migration, as well as EMT. Mir-148a-5p was identified as a target of circSTAM to regulate cell migration and invasion. Mir-148a-5p negatively regulated PTEN expression in trophoblast HTR-8 /SVneo cells.ConclusionIn summary, circSTAM upregulation in PE trophoblasts promoted the invasion, migration and EMT. CircSTAM may modulate trophoblast phenotype by impinging on mir-148a-5p/PTEN axis. These data provided novel insights into the pathogenesis of PE.

Exposure to higher concentrations of exogenous ELABELA causes HTR-8/SVneo trophoblast cell dysfunction: A possible pathogenesis of pre-eclampsia.

Pre-eclampsia (PE) is a multi-system disorder of pregnancy which constitute one of the leading causes of maternal and perinatal mortality worldwide. Dysfunction of trophoblast cells have been play an a significant role in the development and progression of PE. ELABELA (ELA), an endogenous apelin receptor (APJ) ligand, is a hormone secreted by the placenta into circulation, we previously identified ELA and its cognate apelin receptor (APJ) as proteins that are differentially expressed in the placentas of humans with PE. However, a fact known to few about the potential regulatory effects of ELA on the functions of trophoblast cells. In this study, our experiments showed that exogenous ELA did not effectively affect the proliferation and apoptosis of HTR-8/SVneo cells in higher concentrations but inhibited the invasion and migration capabilities. Studies have shown that the epithelial-mesenchymal transition (EMT) event of trophoblast cells is abnormal through regulate the P13K/AKT pathway in PE. First we confirmed APJ expression in HTR-8/SVneo cells and ELA suppressed P13K/AKT signalling pathway-related factors (AKT, phospho (p)-AKT) phosphorylation in HTR-8/SVneo cells in a concentration-dependent manner. Next, we found that treatment with higher concentrations of ELA or the P13K inhibitor LY294002 significantly increased the expression of β-catenin which is the classical epithelial marker relative to the control group. Moreover, treatment with both LY294002 and ELA more strongly affected the β-catenin expression and the HTR8/SVneo cells invasion and migration. These results demonstrate that ELA inhibits trophoblast cell functions by altering the β-catenin expression get though the PI3K/AKT signalling pathway in PE. Thus, this result might provide a new therapeutic target for the treatment of PE.

MiR-101-3p contributes to the progression of preeclampsia by suppressing WDR5-mediated proliferation and invasion of trophoblast.

Decreased proliferation and invasion of trophoblast were proven to be involved in the pathogenesis of preeclampsia (PE). However, the regulatory network has not been clarified yet. This study aimed to explore the role of miR-101-3p in the progression of PE. miR-101-3p expression in placentas of pregnant women with or without PE was analyzed by real-time quantitative PCR (RT-qPCR). Trophoblastic HTR-8/SVneo and HPT-8 cell lines were cultured and underwent hypoxia/reoxygenation (H/R) treatment to mimic PE in vitro. Cell proliferation and invasion were analyzed in gain-of and loss-of-function assays. Finally, we undertook in vivo studies to explore effects of miR-101-3p in the PE model. Compared to placentas from patients without PE, miR-101-3p expressed significantly higher in placentas from PE patients, and its level was positively correlated with the severity of patients. In vitro studies found that overexpression of miR-101-3p significantly suppressed cell proliferation and invasion, while knockdown of miR-101-3p reversed the impacts of H/R treatment. Further research showed that the expression of WD repeat domain 5 (WDR5) was significantly lower in placentas from patients with PE, and its level was negatively associated with the severity of patients. In vitro and in vivo studies confirmed that miR-101-3p promoted PE progression through the regulation of WD WDR5 expression. Increased expression of miR-101-3p in placenta contributes to the development of PE by suppressing WDR5-mediated proliferation and invasion of trophoblast.

MiR-372-3p promotes preeclampsia progression by regulating twist1.

Preeclampsia (PE) is a common pregnancy-related disorder worldwide. PE is mainly characterized by the defective migration and invasion of trophoblast cells. MicroRNAs (miRs) have been reported to serve an important role in PE. The purpose of the study was to explore the pathogenesis and therapeutic targets of preeclampsia. In the present study, reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-372-3p were upregulated in placental tissues from patients with PE. Notably, the expression levels of miR-372-3p were significantly upregulated in patients with early-onset PE compared with patients with late-onset PE. Moreover, in vitro analysis using wound healing, Transwell and western blotting assays demonstrated that miR-372-3p overexpression inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HTR-8/SVneo trophoblast cells, respectively. Bioinformatics analysis and a dual luciferase reporter assay revealed that miR-372-3p is sponged by twist family bHLH transcription factor 1 (twist1). Rescue experiments found that miR-372-3p overexpression suppressed trophoblast cell migration, invasion and EMT by downregulating the expression of twist1. In conclusion, the present study revealed that high level of miR-372-3p may act as a factor to cause PE and may also be a potential novel therapeutic target for PE.

Mitochondrial Dysfunction, Mitophagy and Their Correlation with Perinatal Complications: Preeclampsia and Low Birth Weight.

Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal. Mitophagy is the selective autophagy of mitochondria, eliminating dysfunctional mitochondria in cells by engulfment within double-membraned vesicles. Preeclampsia and low birth weight constitute prenatal complications during pregnancy and are leading causes of maternal and fetal mortality and morbidity. Both placental implantation and fetal growth require a large amount of energy, and a defect in the mitochondrial quality control mechanism may be responsible for the pathophysiology of these diseases. In this review, we compiled current studies investigating the role of BNIP3, DRAM1, and FUNDC1, mediators of receptor-mediated mitophagy, in the progression of preeclampsia and the role of mitophagy pathways in the pathophysiology of low birth weight. Recent studies have indicated that mitochondrial dysfunction and accumulation of reactive oxygen species are related to preeclampsia and low birth weight. However, due to the lack of studies in this field, the results are controversial. Therefore, mitophagy-related pathways associated with these pathologies still need to be elucidated. Mitophagy-related pathways are among the promising study targets that can reveal the pathophysiology behind preeclampsia and low birth weight.

Downregulation of Circ_0088196 Contributes to the Development of Trophoblastic Cells through miR-133b Sponging Function to Affect the AHNAK Expression

Objective: Preeclampsia (PE) is the most common gestational disease related to various biomolecules, including circular RNA. Hsa_circ_0088196 (circ_0088196) was aberrantly upregulated in PE tissues. Design: This study focused on the further exploration of circ_0088196 in PE. Methods: Circ_0088196, microRNA-133b (miR-133b), and AHNAK Nucleoprotein (AHNAK) levels were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). EDU assay was used for proliferation detection. Cell cycle and apoptosis were analyzed using flow cytometry. Wound healing assay and transwell assay were performed to assess migration and invasion. The protein levels were determined via Western blot. Target analysis was conducted through dual-luciferase reporter assay and RNA pull-down assay. Results: Circ_0088196 upregulation was detected in PE patients. The knockdown of circ_0088196 induced the promotion of proliferation, cell cycle, migration, and invasion but not the inhibition of apoptosis in trophoblastic cells. Then, circ_0088196 was found to act as a sponge of miR-133b in HTR-8/SVneo cells. The inhibition of miR-133b abolished the regulation of si-circ_0088196 in trophoblastic cells. In addition, miR-133b targeted AHNAK and circ_0088196 evoked the expression change of AHNAK by sponging miR-133b. The function of circ_0088196 was also achieved by regulating AHNAK in trophoblastic cells. Limitations: The role of circ_0088196 in PE was not verified by in vivo experiments. Conclusion: The current evidence demonstrated that circ_0088196 knockdown facilitated trophoblastic cell development by regulating the levels of miR-133b and AHNAK, suggesting that circ_0088196 promoted the PE progression via the miR-133b/AHNAK axis.

Elevated trophoblastic Siglec6 contributes to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling in preeclampsia

Preeclampsia (PE), a systemic vascular disorder, is the leading cause of maternal and perinatal morbidity and mortality, and its pathogenesis has yet to be fully elucidated. Siglec6, a transmembrane protein, is highly expressed in human placental trophoblasts, and previous studies have shown that Siglec6 overexpression correlates with PE, but the role of Siglec6 during PE progression is unknown. Here, we demonstrated that the mRNA and protein expression levels of Siglec6 were upregulated in early-onset PE placentas compared with uncomplicated pregnancies, and Siglec6 was primarily located in syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). Moreover, our results showed that chemical reagent-induced HIF-1α accumulation promoted the mRNA and protein levels of Siglec6 in HTR8/SVneo and BeWo cells. Although Siglec6 overexpression did not affect HTR8/SVneo cell proliferation, migration, and invasion, the conditional medium derived from the Siglec6 overexpressed HTR8/SVneo cells (Siglec6-OE-CM) significantly impaired the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, the transcriptome sequencing results revealed that Siglec6 overexpression led to the downregulation of Wnt6 in HTR8/SVneo cells, which was further confirmed by qPCR and ELISA. Recombinant human Wnt6 reversed Siglec6-OE-CM-mediated suppression of HUVEC functions by reactivating the Wnt/β-catenin signaling pathway. Altogether, our study found that elevated trophoblastic Siglec6 contributed to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling.

Circ_0077109 sponges miR-139-5p and upregulates HOXD10 in trophoblast cells as potential mechanism for preeclampsia progression.

One of the important reasons for the development of preeclampsia (PE) is the abnormal function of trophoblast cells. Many circular RNAs (circRNAs) have been confirmed to participate in the regulation of trophoblast cell function to mediate PE progression. However, whether circ_0077109 is involved in PE progression through regulating trophoblast cell function remains unclear. Quantitative real-time PCR was utilized for measuring the expression of circ_0077109, microRNA (miR)-139-5p and homeobox D10 (HOXD10). Trophoblast cell proliferation, apoptosis, invasion, and angiogenesis was assessed cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and tube formation assay. In addition, western blot analysis was used to determine protein expression. The interaction between miR-139-5p and circ_0077109 or HOXD10 was verified by dual-luciferase reporter assay and RIP assay. Our results pointed out that circ_0077109 was a circRNA with upregulated expression in PE patients. Overexpression of circ_0077109 suppressed trophoblast cell proliferation, invasion, and angiogenesis, while increased apoptosis. MiR-139-5p was found to be sponged by circ_0077109, and its mimic reversed the suppressive effect of circ_0077109 on trophoblast cell function. HOXD10 was a target of miR-139-5p, and its overexpression inhibited trophoblast cell proliferation, invasion, and angiogenesis. MiR-139-5p inhibitor could repress trophoblast cell function, while this effect could be reversed by HOXD10 knockdown. In summary, we confirmed that circ_0077109 inhibited trophoblast cell function through the regulation of miR-139-5p/HOXD10 axis, which might be a potential target for PE treatment.

Inflammasome activation in preeclampsia and intrauterine growth restriction.

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8%-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR. In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples versus NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR.

A novel regulated network mediated by downregulation HIF1A-AS2 lncRNA impairs placental angiogenesis by promoting ANGPTL4 expression in preeclampsia.

Preeclampsia (PE) is the predominant medical condition leading to maternal and fetal mortality, and the lack of effective treatment increases its risk to the public health. Among the numerous predisposing factors, the ineffectual remodeling of the uterine spiral arteries, which can induce abnormal placental angiogenesis, has been focused to solve the pathogenesis of PE. According to the preceding research results, abnormal expression of long non-coding RNAs (lncRNA)s could be associated with the pathological changes inducing PE. To be more specific, lncRNA HIF1A-AS2 was proposed for its potential to participate in the molecular mechanisms underlying PE. In vitro, in trophoblast cell lines HTR-8/SVneo and human umbilical vein endothelial cells HUVECs, HIF1A-AS2 knockdown inhibited cell proliferation, migration and tube formation. Mechanistically, transcription factor FOXP1 could regulate the expression of HIF1A-AS2. Moreover, a series of assays, including RNA pull down and mass spectrometry, RNA immunoprecipitation and chromatin immunoprecipitation assay, revealed that HIF1A-AS2 interacted with Lamin A/C (LMNA) to inhibit ANGPTL4 expression in trophoblast cells, thus further participating in the progression of PE. Taken together, these findings suggested that further analysis on HIF1A-AS2 could contribute to the development of prospective therapeutic strategy for PE.

LncRNA-loc391533 is involved in the progression of preeclampsia through VEGF.

Preeclampsia (PE) is a leading cause of maternal death worldwide, which is one of the most major pregnancy complications. The effects of vascular endothelial growth factor (VEGF) and lncRNA-loc391533 on PE were evaluated in the present study. Expression of VEGF in pregnant women with PE was determined using immunohistochemical and enzyme linked immunosorbent assay (ELISA). The effects of lncRNA-loc391533 knockdown and overexpression on VEGF expression was detected using quantitative polymerase chain reaction (qPCR) and western blotting. Loss/gain-of-function assays were performed to evaluate the role of lncRNA-loc391533 on proliferation, cell cycle and migration of trophoblasts HTR-8/SVneo cells. We found that VEGF and its receptor VEGFR1/2 were low expressed in PE. Knockdown of lncRNA-loc391533 enhanced VEGF expression, while overexpression of lncRNA-loc391533 downregulated VEGF. Moreover, lncRNA-loc391533 was required for proliferation and migration of HTR-8/SVneo cells. In conclusion, our findings emphasized that lncRNA-loc391533 exhibited a critical role in progression of PE through VEGF, which might as a novel therapeutic target for PE treatment.