Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Wang, Hao; Wang, Pan; Liang, Xiaoling; Li, Wenjing; Yang, Mei; Ma, Jinlong; Wei, Yunrong; Fan, Shang­rong

doi:10.1111/jcmm.15011

Cited by 9 publications

(14 citation statements)

References 54 publications

(86 reference statements)

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“…In contrast to the data presented herein, one previous study found placental EPCR markedly reduced in preeclamptic patients 13 . However, it is important to note that their patient samples had been derived from women with the onset of term preeclampsia, whereas our present study focused mainly on preterm disease.…”

Section: Discussioncontrasting

confidence: 70%

“…In contrast to the data presented herein, one previous study found placental EPCR markedly reduced in preeclamptic patients. 13 However, it is important to note that their patient samples had been derived from women with the onset of term preeclampsia, whereas our present study focused mainly on preterm disease. It has been speculated that the underlying etiology and pathophysiology differ between the preeclamptic phenotypes, 32 therefore, the underlying defects contributing to term disease may not be the same as those in preterm disease.…”

Section: Discussionmentioning

confidence: 99%

“…Given pregnancy is associated with important changes to the coagulation pathway, 12 abnormalities in pathways such as that of protein C, maybe a potential risk factor for maternal and fetal health, resulting in pregnancy complications 12 . A previous study suggested EPCR levels were reduced in preeclamptic placenta, 13 while abnormal plasma levels of soluble EPCR have also been reported 14,15 . However, our understanding of the role of EPCR in the placenta and its possible contribution to the pathogenesis of preeclampsia and/or fetal growth restriction is limited and requires further study.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction

et al. 2022

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Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize endothelial protein C receptor (EPCR) in preterm preeclampsia, term preeclampsia, and fetal growth restriction (defined by delivery of a small for gestational age [SGA] infant [<10% birthweight centile]) and examine its regulation in primary syncytiotrophoblast. Placental EPCR mRNA and protein were significantly increased in patients with preterm preeclampsia (<34 weeks gestation) compared to gestation-matched controls (p < .0001). In the plasma, EPCR was also significantly elevated (p = .01) in established preterm preeclampsia while its substrate, protein C (PC) was significantly reduced (p = .0083). Placentas from preterm small for gestational age (SGA) cases, had elevated EPCR mRNA expression (p < .0001) relative to controls. At 36 weeks, no significant changes in plasma EPCR were detected in samples from

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction

et al. 2022

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“…Studies have revealed that F2R is responsible for thrombin-induced sFlt-1 and IL-11 expression and regulates the migration of extravillous trophoblast cells [71,72]. Wang et al [73] revealed that the downregulation of endothelial protein C receptor (EPCR) expression leads to decreased proliferation, invasion, and tube formation of trophoblasts by the rearrangement of actin through the F2R/Rac1 signaling pathway in PE. It has been shown that EPCR can directly bind to F2R and plays a role in the process of F2R activation [74].…”

Section: Discussionmentioning

confidence: 99%

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis

Wang

Yang

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Preeclampsia (PE) is a multisystemic syndrome which has short- and long-term risk to mothers and children and has pluralistic etiology. Objective. This study is aimed at constructing a competitive endogenous RNA (ceRNA) network for pathways most related to PE using a data mining strategy based on weighted gene coexpression network analysis (WGCNA). Methods. We focused on pathways involving hypoxia, angiogenesis, and epithelial mesenchymal transition according to the gene set variation analysis (GSVA) scores. The gene sets of these three pathways were enriched by gene set enrichment analysis (GSEA). WGCNA was used to study the underlying molecular mechanisms of the three pathways in the pathogenesis of PE by analyzing the relationship among pathways and genes. The soft threshold power (β) and topological overlap matrix allowed us to obtain 15 modules, among which the red module was chosen for the downstream analysis. We chose 10 hub genes that satisfied ∣ log 2 Fold Change ∣ > 2 and had a higher degree of connectivity within the module. These candidate genes were subsequently confirmed to have higher gene significance and module membership in the red module. Coexpression networks were established for the hub genes to unfold the connection between the genes in the red module and PE. Finally, ceRNA networks were constructed to further clarify the underlying molecular mechanism involved in the occurrence of PE. 56 circRNAs, 17 lncRNAs, and 20 miRNAs participated in the regulation of the hub genes. Coagulation factor II thrombin receptor (F2R) and lumican (LUM) were considered the most relevant genes, and ceRNA networks of them were constructed. Conclusion. The microarray data mining process based on bioinformatics methods constructed lncRNA and miRNA networks for ten hub genes that were closely related to PE and focused on ceRNAs of F2R and LUM finally. The results of our study may provide insight into the mechanisms underlying PE occurrence.

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“…Protein C binds to mEPCR with high affinity, and is converted to activated protein C (APC) by the thrombin–thrombomodulin complex on the surface of endothelial cells through a limited proteolytic process ( 17 ). The mEPCR variant can bind to APC and plays important roles in anticoagulation, anti-inflammatory, cell protection (anti-apoptosis), protecting endothelial barrier function, and promoting neovascularization ( 18 – 22 ). When activated by the thrombin–thrombomodulin complex, APC dissociates from the membrane-bound receptor mEPCR, and functions as an anticoagulant by inactivating coagulation factors Va and VIIIa ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome

Cai

Hao

Chen

et al. 2022

Front. Cardiovasc. Med.

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BackgroundChronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification.MethodsData-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort.ResultsFifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone.ConclusionPlasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.

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Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Cited by 9 publications

References 54 publications

Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction

Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome

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