scholarly journals Involvement of Angiopoietin-2 and Tie2 Receptor Phosphorylation in STEC-HUS Mediated byEscherichia coliO104:H4

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alexander Lukasz ◽  
Jan Beneke ◽  
Kristina Thamm ◽  
Jan T. Kielstein ◽  
Jan Menne ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Endothelial Activation ◽  
Receptor System ◽  
Tie2 Receptor ◽  
Mediator Role ◽  
Uremic Syndrome ◽  
Umbilical Vein Endothelial Cells ◽  
Angiopoietin 2

Escherichia coliO104:H4-associated hemolytic uremic syndrome (HUS) is characterized by Shiga toxin-induced vascular damage. As indicated by recent studies, dysregulation of the angiopoietin (Angpt)/Tie2 ligand receptor system may be crucial for endothelial dysfunction in HUS. Early Angpt-2 levels quantified in 48 adult HUS patients were predictive for a complicated clinical course, in particular for need of hemodialysis and mechanical ventilation as well as occurrence of seizures.In vitrochallenge of human umbilical vein endothelial cells with patients’ sera indicated an injurious mediator role of Angpt-2 opening future perspectives for mitigating endothelial activation in HUS.

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

scholarly journals A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jing-Shang Wang ◽  
Ye Huang ◽  
Shuping Zhang ◽  
Hui-Jun Yin ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Level ◽  
Umbilical Vein ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

Generation and role of angiostatin in human platelets

Blood ◽  
2003 ◽  
Vol 102 (9) ◽  
pp. 3217-3223 ◽  
Author(s):  
Paul Jurasz ◽  
David Alonso ◽  
Susana Castro-Blanco ◽  
Ferid Murad ◽  
Marek W. Radomski
Keyword(s):  
Umbilical Vein ◽  
Blood Clot ◽  
Active Form ◽  
Angiogenesis Inhibitor ◽  
Human Platelets ◽  
Healthy Human ◽  
Vessel Growth ◽  
Umbilical Vein Endothelial Cells

AbstractPlatelets regulate new blood vessel growth, because they contain a number of angiogenesis promoters and inhibitors. Additionally, platelets contain matrix metalloproteinases (MMPs), which when released mediate platelet adhesion and aggregation, and plasminogen, a fibrinolytic system enzyme that serves to limit blood clot formation. Enzymatic cleavage of plasminogen by MMPs generates angiostatin, an angiogenesis inhibitor. Therefore, we examined whether platelets generate angiostatin during aggregation in vitro. Platelets were isolated from healthy human donors and then aggregated with collagen, thrombin, or HT-1080 fibrosarcoma cells. Angiostatin was detected by Western blot analysis in the platelet releasates of all blood donors irrespective of the aggregating agent used. Platelet pellet homogenates showed the presence of angiostatin in all donors, which was released upon aggregation. Furthermore, platelet-derived angiostatin was isolated and purified by lysine-Sepharose affinity chromatography from collagen-aggregated platelet releasates. Bioassay of platelet-derived angiostatin showed that it inhibited the formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in an in vitro angiogenesis model. Inhibition of angiostatin in platelet releasates promoted the formation of capillary structures by HUV-EC-Cs. We conclude that healthy human platelets contain angiostatin, which is released in active form during platelet aggregation, and platelet-derived angiostatin has the capacity to inhibit angiogenesis.

Endothelial CSN5 impairs NF-κB activation and monocyte adhesion to endothelial cells and is highly expressed in human atherosclerotic lesions

2013 ◽  
Vol 110 (07) ◽  
pp. 141-152 ◽  
Author(s):  
Yaw Asare ◽  
Erdenechimeg Shagdarsuren ◽  
Johannes Schmid ◽  
Pathricia Tilstam ◽  
Jochen Grommes ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Negative Regulator ◽  
Multifunctional Protein ◽  
Atherosclerotic Lesions ◽  
Tnf Α ◽  
Reporter Assays ◽  
Umbilical Vein Endothelial Cells

SummaryThe COP9 signalosome (CSN), a multifunctional protein complex involved in the regulation of cullin-RING-E3 ubiquitin ligases (CRLs), has emerged as a regulator of NF-κB signalling. As NF-κB drives the expression of pro-inflammatory and pro-atherosclerotic genes, we probed the yet unknown role of the CSN, in particular CSN5, on NF-KB-mediated atherogenic responses in endothelial cells. Co-immunoprecipitation in human umbilical vein endothelial cells (HUVECs) revealed the presence of a super-complex between IKK and CSN, which dissociates upon TNF-α stimulation. Furthermore, CSN5 silencing enhanced TNF-α-induced IKB-α degradation and NF-κB activity in luci-ferase reporter assays. This was paralleled by an increased NF-KB-driven upregulation of atherogenic chemokines and adhesion molecules, as measured by qPCR and flow cytometry, and translated into an enhanced arrest of THP-1 monocytes on TNF-α-stimulated, CSN5-depleted HUVECs. Reverse effects on NF-κB activity and THP-1 arrest were seen upon CSN5 overexpression. Finally, double-immunostaining confirmed the expression of CSN subunits in the endothelium of human atherosclerotic lesions, and revealed an increased expression of CSN5 which correlated with atheroprogression. In conclusion, endothelial CSN5 attenuates NF-KB-dependent pro-inflammatory gene expression and monocyte arrest on stimulated endothelial cells in vitro, suggesting that CSN5 might serve as a negative regulator of atherogenesis.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.

Cyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells

2003 ◽  
Vol 104 (4) ◽  
pp. 421-428 ◽  
Author(s):  
Hang CHANG ◽  
Bao-Wei WANG ◽  
Peiliang KUAN ◽  
Kou-Gi SHYU
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Mechanical Stretch ◽  
Receptor Proteins ◽  
Herbimycin A ◽  
Tie2 Receptor ◽  
Kinase C ◽  
Umbilical Vein Endothelial Cells ◽  
Angiopoietin 2 ◽  
Angiopoietin 1

Endothelial cells are essential for neovascularization. Angiopoietins and Tie receptors are required for a normal vasculature. How cyclical mechanical stretch affects the expression of components of the angiopoietin system is not known. In this study, we investigated the regulation of angiopoietins and Tie receptors by cyclical mechanical stretch in cultured human umbilical vein endothelial cells (HUVECs). HUVECs grown on a flexible membrane base were stretched by vacuum to 20% elongation, at 60cycles/min. The levels of angiopoietin-2 protein began to increase as early as 2h after stretch was initially applied, reached a maximum of 2.7-fold over the control value by 6h. The Tie2 receptor protein showed the same pattern as Ang-2. These increases in angiopoietin-2 and Tie2 receptor proteins at 6h were blocked by the addition (30min before stretch) of the protein kinase C inhibitor Gö6976 (16nM) or the tyrosine kinase inhibitor herbimycin A (24µM). Similar to protein expression, the levels of angiopoietin-2 and Tie2 receptor mRNAs in HUVECs increased 3.1-fold and 2.5-fold respectively after stretch for 6h. These increases were also blocked by Gö6976 or herbimycin A. Cyclical mechanical stretch increased (and Gö6976 or herbimycin A abrogated these increases) the immunohistochemical labelling of angiopoietin-2 and Tie2 receptor after a 6h stretch. The levels of angiopoietin-1 and Tie1 receptor proteins, mRNAs and immunohistochemical staining were unaffected by cyclical mechanical stretch. Thus cyclical mechanical stretch activates the expression of angiopoietin-2 and the Tie2 receptor, but not angiopoietin-1 or the Tie1 receptor, in cultured HUVECs. This mechanical effect is probably mediated by the tyrosine kinase and protein kinase C pathways.

scholarly journals Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro

2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Qiang Wu ◽  
Shunxiang Xu ◽  
Fei Wang ◽  
Bo He ◽  
Xin Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Umbilical Vein ◽  
Alkaline Condition ◽  
Akt Signaling Pathway ◽  
Alkaline Environment ◽  
Umbilical Vein Endothelial Cells ◽  
Adverse Factor

Abstract Magnesium (Mg) is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo, however, the inherent alkalinity is the adverse factor that needs further attention. In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro, magnesium-silicocarnotite [Mg-Ca5(PO4)2SiO4, Mg-CPS] was designed and fabricated. In this study, Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10 wt.% magnesium oxide (MgO), since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro. Besides, provided that MgO was incorporated with 15 wt.% in CPS, the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions, stronger alkalinity and lower Ca/P/Si ions caused. According to the results, it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects, which were the consequence of Mg ions and alkaline environment combined. Therefore, if MgO is properly incorporated in CPS, the improved bioactivities could cover alkaline adversity, making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro.

scholarly journals The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1

2016 ◽  
Vol 38 (2) ◽  
pp. 502-513 ◽  
Author(s):  
Fei Shi ◽  
Tian-Zhi Zhao ◽  
Yong-Chun Wang ◽  
Xin-Sheng Cao ◽  
Chang-Bin Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Microgravity Environment ◽  
Caveolin 1 ◽  
Endothelial Functions ◽  
Umbilical Vein Endothelial Cells ◽  
The Impact

Background/Aims: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. Methods: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. Results: We found that decreased caveolin-1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. Conclusion: Our study provides insight for the important endothelial functions in altered gravitational environments.

MSCs inhibits the angiogenesis of HUVECs through the miR-211/Prox1 pathway

2019 ◽  
Vol 166 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Jian Pan ◽  
Xianglong Wang ◽  
Dequan Li ◽  
Jianmin Li ◽  
Zipei Jiang
Keyword(s):  
Umbilical Vein ◽  
Critical Role ◽  
Corneal Opacity ◽  
Corneal Neovascularization ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Prox1 Expression ◽  
Umbilical Vein Endothelial Cells

Abstract The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) on the angiogenesis of human umbilical vein endothelial cells (HUVECs). MSCs were subconjunctival injected into rat corneal alkali burn models. Their impacts on the degree of corneal neovascularization (CNV) and corneal opacity were evaluated at 3, 6, 9 and 12 days after injection. An in vitro experiment of MSCs affecting HUVECs angiogenesis was performed and evaluated using the tube formation assay. The results showed that both CNV and corneal opacity were decreased in rats after MSCs injection. In HUVECs, angiogenesis of cells was inhibited by miR-211 overexpression. miR-211 negatively regulated Prox1 expression. Knockdown of miR-211 blocked the decrease of Prox1 expression induced by MSCs and the inhibitory effect of MSCs on the angiogenesis of HUVECs. The critical role of miR-211 in MSCs inhibition of corneal angiogenesis was confirmed in rat experiments. We concluded that MSCs inhibited the angiogenesis of HUVEC through miR-211 mediating the down-regulation of Prox1.

scholarly journals Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuang-Shuang Dong ◽  
Dan-Dan Dong ◽  
Zhang-Fu Yang ◽  
Gui-Qi Zhu ◽  
Dong-Mei Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Transmission Electron ◽  
Umbilical Vein Endothelial Cells ◽  
Hcc Cells

BackgroundAngiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated.Methods and ResultsExosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively. In vitro and in vivo analyses showed that exosomes isolated from highly metastatic HCC cells enhanced the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) compared to exosomes derived from poorly metastatic HCC cells. In addition, microarray analysis of HCC-Exos was conducted to identify potential functional molecules, and miR-3682-3p expression was found to be significantly downregulated in exosomes isolated from highly metastatic HCC cells. By in vitro gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis.ConclusionOur study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.

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