scholarly journals IL-33 / ST2 Signaling Promotes TF Expression by Regulating NF-κB Activation in Coronary Artery Endothelial Microparticles

2021 ◽  
Author(s):  
Yujuan Yuan ◽  
Hui Cheng ◽  
Jing Tao ◽  
Muyesai Nijiati
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Stable Coronary Artery Disease ◽  
Dimethyl Fumarate ◽  
Human Coronary Artery ◽  
Roc Curve Analysis ◽  
Endothelial Microparticles ◽  
Artery Disease ◽  
St2 Receptor

IntroductionInterleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial Microparticles(EMPs). Tissue factor (TF) plays a central role in hemostasis and thrombosis.Material and methodsThe study analyzed the coronary blood of level of CD31+EMPs, TF protein and IL-33 protein in Acute Myocardial Infarction (AMI) and stable coronary artery disease (SCAD) patients. Human coronary artery endothelial cells (HCAECs) were treated with IL-33 to obtain EMPs. The TF activity of EMPs was tested by Thermo Fisher by adding the TF antibody. Furthermore, TF and Tissue Factor Pathway Inhibitor (TFPI) protein were tested by ELISA. Finally, NF-κB inhibitor dimethyl fumarate (DMF) and soluble extracellular domain of ST2 coupled to the Fc fragment of human IgG1 (sST2) were added to HCAECs which were treated with IL-33, and the TF protein level was also tested by ELISA.ResultsThe AMI patients had higher level of CD31+EMPs, TF protein and IL-33 protein than the SCAD patients in coronary artery. In AMI patients (N=27), the IL-33 protein positively correlated with CD31+EMPs (r=0.794, p<0.01). According to the ROC curve analysis, the AUC of CD31+EMPs, TF protein and IL-33 protein were 0.888, 0.962 and 0.778 respectively. In the cell culture, the TF activity and TF protein in EMPs increased gradually with time of intervention by the treatment of IL-33. IL-33 binding to the ST2 receptor promoted TF expression by regulating NF-κB activation in EMPs of HCAECs.ConclusionsActivated endothelial cells and EMPs they released simultaneously express TF, which is a risk factor for cardiovascular disease.

scholarly journals IL-33 / ST2 Signaling Promotes TF Expression by Regulating NF-κB Activation in Coronary Artery Endothelial Microparticles of Acute Myocardial Infarction

2020 ◽  
Author(s):  
Yujuan Yuan ◽  
Hui Cheng ◽  
Jing Tao ◽  
Nijiati Muyesai
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Dimethyl Fumarate ◽  
Human Coronary Artery ◽  
Roc Curve Analysis ◽  
Artery Disease ◽  
St2 Receptor

Abstract Background: Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells derived Microparticles（EMPs）. Tissue factor (TF) plays a central role in hemostasis and thrombosis. Objective: The aim of this study was to investigate the effect of IL-33 on TF release of EMPs, which may be a new link between inflammation and coagulation. Methods: The study analyzed the coronary blood of level of CD31+EMPs, TF protein and IL-33 protein in acute myocardial infarction(AMI) and stable coronary artery disease(SCAD) patients. Human coronary artery endothelial cells (HCAECs) were treated with IL-33 to obtain MPs. The TF activity of EMPs was tested by thermo fisher by adding the TF antibody. Furthermore, TF and TFPI protein were tested by ELISA. Finally, NF-κB inhibitor dimethyl fumarate (DMF) and soluble extracellular domain of ST2 coupled to the Fc fragment of human IgG1 (sST2) were added HCAECs, which were treated with IL-33, then the TF protein level also was tested by ELISA. Results: The AMI patients have higher level of CD31+EMPs, TF protein and IL-33 protein than the SCAD patients in coronary blood. In AMI patients (N=27) , the IL-33 protein positively correlated with CD31+EMPs (r = 0.794, p < 0.01). According to the ROC curve analysis, the areas under the curve (AUC) of CD31+EMPs, TF protein and IL-33 protein were 0.888, 0.962 and 0.778. In the cell culture, the TF activity and TF protein in ECs-derived MPs increased gradually with time of intervention by the treatment of IL-33. IL-33 binding to the ST2 receptor promoted TF expression by regulating NF-κB activation in ECs-derived MPs of HCAECs. Conclusion: Activated endothelial cells and their released MPs simultaneously express TF, which is a risk factor for cardiovascular disease.

scholarly journals The Ratio of Factor VIIa:Tissue Factor Content within Microvesicles Determines the Differential Influence on Endothelial Cells

TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e132-e145 ◽  
Author(s):  
Yahya Madkhali ◽  
Sophie Featherby ◽  
Mary Collier ◽  
Anthony Maraveyas ◽  
John Greenman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Cellular Proliferation ◽  
Molar Ratio ◽  
Activity Levels ◽  
Human Coronary Artery ◽  
Determining Factors ◽  
Mcf 7

AbstractTissue factor (TF)-positive microvesicles from various sources can promote cellular proliferation or alternatively induce apoptosis, but the determining factors are unknown. In this study the hypothesis that the ratio of fVIIa:TF within microvesicles determines this outcome was examined. Microvesicles were isolated from HepG2, BxPC-3, 786-O, MDA-MB-231, and MCF-7 cell lines and microvesicle-associated fVIIa and TF antigen and activity levels were measured. Human coronary artery endothelial cells (HCAECs) were incubated with these purified microvesicles, or with combinations of fVIIa-recombinant TF, and cell proliferation/apoptosis was measured. Additionally, by expressing mCherry-PAR2 on HCAEC surface, PAR2 activation was quantified. Finally, the activation of PAR2 on HCAEC or the activities of TF and fVIIa in microvesicles were blocked prior to addition of microvesicles to cells. The purified microvesicles exhibited a range of fVIIa:TF ratios with HepG2 and 786-O cells having the highest (54:1) and lowest (10:1) ratios, respectively. The reversal from proapoptotic to proliferative was estimated to occur at a fVIIa:TF molar ratio of 15:1, but HCAEC could not be rescued at higher TF concentrations. The purified microvesicles induced HCAEC proliferation or apoptosis according to this ruling. Blocking PAR2 activation on HCAEC, or inhibiting fVIIa or TF-procoagulant function on microvesicles prevented the influence on HCAEC. Finally, incubation of HCAEC with recombinant TF resulted in increased surface exposure of fVII. The induction of cell proliferation or apoptosis by TF-positive microvesicles is dependent on the ratio of fVIIa:TF and involves the activation of PAR2. At lower TF concentrations, fVIIa can counteract the proapoptotic stimulus and induce proliferation.

Abstract 190: Purinergic Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: New AP-1 Site and Negative Regulator

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yiwei Liu ◽  
Lingxin Zhang ◽  
Chuan Wang ◽  
Shama Roy ◽  
Jianzhong Shen
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Promoter Activity ◽  
Purinergic Receptor ◽  
Consensus Sequence ◽  
Negative Regulator ◽  
Coagulation Cascade ◽  
Human Coronary Artery

Previously we reported that the P2Y2 receptor (P2Y2R) is one of the predominant purinergic receptors expressed in human coronary artery endothelial cells (HCAEC), and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here we report a role of a newly identified AP-1 consensus sequence along with its new binding components in P2Y2R regulation of TF transcription. We identified with bioinformatics tools that a novel AP-1 site at -1363 bp of human TF promoter region is highly conserved across multiple species. P2Y2R activation increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this new distal AP-1 site all significantly supressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2 and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2, but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation, leading to Fra-1 activation while JNK activated c-Jun and ATF-2. These findings reveal the basis for P2Y purinergic receptor regulation of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy in control of vascular thrombogenicity and/or inflammation associated with endothelial dysfunction.

The adipokine visfatin induces tissue factor expression in human coronary artery endothelial cells

2012 ◽  
Vol 130 (3) ◽  
pp. 403-408 ◽  
Author(s):  
Plinio Cirillo ◽  
Vito Di Palma ◽  
Fabio Maresca ◽  
Francesco Pacifico ◽  
Francesca Ziviello ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Human Coronary Artery ◽  
Factor Expression

scholarly journals Reciprocal regulation of endothelial–mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Byambasuren Vanchin ◽  
Marloes Sol ◽  
Rutger A. F. Gjaltema ◽  
Marja Brinker ◽  
Bianca Kiers ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Intimal Hyperplasia ◽  
Human Coronary Artery ◽  
Mesenchymal Transition ◽  
Ezh2 Expression ◽  
Artery Disease ◽  
Human Coronary Artery Disease ◽  
Endothelial Mesenchymal Transition

AbstractEndothelial–mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFβ1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.

Adipocytokine resistin induces tissue factor expression in human coronary artery endothelial cells via NF kB-dependent pathway

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. 4370-4370
Author(s):  
P. Calabro ◽  
L. Riegler ◽  
P. Cirillo ◽  
F. Fimiani ◽  
G. Limongelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Human Coronary Artery ◽  
Factor Expression ◽  
Dependent Pathway

scholarly journals Purinergic P2Y2 Receptor Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells

2015 ◽  
Vol 291 (4) ◽  
pp. 1553-1563 ◽  
Author(s):  
Yiwei Liu ◽  
Lingxin Zhang ◽  
Chuan Wang ◽  
Shama Roy ◽  
Jianzhong Shen
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Promoter Activity ◽  
Consensus Sequence ◽  
Coagulation Cascade ◽  
Loss Of Function ◽  
P2y2 Receptor ◽  
Human Coronary Artery

We recently reported that the P2Y2 receptor (P2Y2R) is the predominant nucleotide receptor expressed in human coronary artery endothelial cells (HCAEC) and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), a key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here, we report the role of a newly identified AP-1 consensus sequence in the TF gene promoter and its original binding components in P2Y2R regulation of TF transcription. Using bioinformatics tools, we found that a novel AP-1 site at −1363 bp of the human TF promoter region is highly conserved across multiple species. Activation of P2Y2R increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this distal AP-1 site all significantly suppressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2, and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2 but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation through Src, leading to Fra-1 activation, whereas Rho/JNK mediated P2Y2R-induced activation of c-Jun and ATF-2. These findings reveal the molecular basis for P2Y G protein-coupled receptor control of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy for controlling vascular inflammation and thrombogenicity associated with endothelial dysfunction.

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