scholarly journals Salmon consumption by pregnant women reduces ex vivo umbilical cord endothelial cell activation

2011 ◽  
Vol 94 (6) ◽  
pp. 1418-1425 ◽  
Author(s):  
Lieke WJ van den Elsen ◽  
Paul S Noakes ◽  
Martin A van der Maarel ◽  
Lefkothea-Stella Kremmyda ◽  
Maria Vlachava ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Pregnant Women ◽  
Umbilical Cord ◽  
Cell Activation ◽  
Ex Vivo ◽  
Endothelial Cell Activation

309 PRODUCTION OF PIGS TRANSGENIC FOR HUMAN HEMEOXYGENASE-I BY SOMATIC NUCLEAR TRANSFER

2008 ◽  
Vol 20 (1) ◽  
pp. 234 ◽  
Author(s):  
B. Petersen ◽  
A. Lucas-Hahn ◽  
D. Herrmann ◽  
W. A. Kues ◽  
W. Ramackers ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Nuclear Transfer ◽  
Cell Activation ◽  
Ex Vivo ◽  
Endothelial Cell Activation ◽  
Transgenic Pigs ◽  
Term Survival ◽  
Transgenic Expression ◽  
Ex Vivo Perfusion ◽  
Somatic Nuclear Transfer

The hyperacute rejection after porcine-to-human xenotransplantation can now be reliably overcome either by transgenic expression of complement regulating factors or by knocking out the gene for α1,3-galactosyltransferase in pigs. The next immunological hurdle is the acute vascular rejection (AVR) primarily caused by endothelial cell activation. Human hemeoxygenase-I (hHO-I) is known to have anti-apoptotic and cell-protective properties. Thus, the expression of hHO-I on porcine endothelial cells could have beneficial effects in a xenotransplantation setting to prevent the formation of AVR. Here we describe the first transgenic pigs with functional expression of hHO-I. Fibroblasts were obtained by an ear punch from a decay accelerating factor (DAF)-transgenic female pig and were cultured in vitro (Kues WA et al. 2005 Biol. Reprod. 72, 1020–1028). Cells reaching confluency of 70 to 80% were detached with EDTA/trypsin and subsequently transfected by electroporation at 450V/350 µF with a vector coding for hHO-I driven by the SV40 promoter. Transfected cells were selected for resistance against G418 (800 µg mL–1) for 14 days. Resistant cell clones were screened for integration of the vector by PCR. One positive cell clone that showed strong expression of the transgene, as determined by immunostaining, was selected for somatic nuclear transfer (Hoelker M et al. 2005 Cloning Stem Cells 7, 35–44). In total, 205 reconstructed embryos were transferred to 2 synchronized peripuberal German Landrace gilts, which gave birth to 9 live piglets, all with normal birth weights. PCR and Southern blot analyses revealed that all of the offspring had integrated the vector into their genome. Two transgenic animals were sacrificed for further characterization and ex vivo perfusion experiments. In these animals, Northern blotting showed weak transcription of the transgene in all xenorelevant organs such as heart, kidney, and liver. Immunostaining of the kidneys revealed that expression of the transgene was confined to the endothelial cell layer. These hHO-I-transgenic porcine kidneys were subjected to an ex vivo perfusion assay and survived ex vivo perfusion for 240 min with AB-pooled human blood, whereas perfusion of 2 non-transgenic controls had to be terminated after 60 min due to problems attributed to immunological rejection. Histology revealed that perfused hHO-I-transgenic kidneys exhibited no indication for xenogenic activation of the human coagulation system. These preliminary results show that functional hHO-I can be expressed in transgenic pigs and that transgenic expression of hHO-I might improve long-term survival of porcine xenografts. These results are encouraging and warrant further studies on endothelial cell activation and the biological function of hemeoxygenase-I in the context of xenotransplantation. This study was funded by the Deutsche Forschungsgemeinschaft Ni 256/22-1, -2, -3.

scholarly journals Inhibitory Effects of Syzygium jambos Extract on Biomarkers of Endothelial Cell Activation

2021 ◽  
Author(s):  
Yaritza Inostroza-Nieves ◽  
Shirley Valentin-Berrios ◽  
Christopher Vega ◽  
Gregory N. Prado ◽  
Claribel Luciano-Montalvo ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Line ◽  
Cell Activation ◽  
Ex Vivo ◽  
Human Endothelial Cell ◽  
Endothelial Cell Activation ◽  
Endothelial Cell Function ◽  
Endothelial Cell Line ◽  
Syzygium Jambos ◽  
Human Endothelial Cell Line

Abstract Background: Disordered endothelial cell activation plays an important role in the pathophysiology of atherosclerosis, cancer, sepsis, viral infections, and inflammatory responses. There is interest in developing novel therapeutics to regulate endothelial cell function in atherothrombotic, metabolic, vascular, and hematological diseases. Extracts from leaves of the Syzygium jambos (L.) Alston (S. jambos) trees have been proposed to treat cardiovascular diseases and diabetes through unclear mechanisms. We investigated the effects of the S. jambos extract on biomarkers of endothelial dysfunction and immune responses in the human endothelial cell line, EA.hy926. Methods: Leaves of S. jambos were collected, concocted and lyophilized. To study the effects of S. jambos on endothelial cell activation, we used the human endothelial cell line. IL-6 levels were measured using qPCR and ELISA. PDI activity was measured using Insulin Turbidity and Di-E-GSSG assays. CM-H2DCFDA was used to study ROS levels. Migration assay was used to study S. jambos effect on ex vivo human polymorphonuclear and human mononuclear cells.Results: Our results show that incubation of EA.hy926 cells with ET-1 led to a 6.5 ± 1.6 fold increase in IL-6 expression by qPCR, an event that was blocked by S. jambos. Also, we observed that ET-1 increased extracellular protein disulfide isomerase (PDI) activity that was likewise dose-dependently blocked by S. jambos (IC50=14µg/mL). Consistent with these observations, ET-1 stimulated ex vivo human polymorphonuclear and mononuclear cell migration that also was dose-dependently blocked by S. jambos. In addition, ET-1 stimulation led to significant increases in ROS production that were sensitive to S. jambos. Conclusion: Our results suggest that the S. jambos extract represents a novel cardiovascular protective pharmacological approach to regulate endothelial cell activation, IL-6 expression, and immune-cell responses.

scholarly journals Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jinglong Tang ◽  
Wenting Cheng ◽  
Jinling Gao ◽  
Yanting Li ◽  
Ruyong Yao ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Carbon Black ◽  
Cell Activation ◽  
Disease Risk ◽  
Ex Vivo ◽  
Engineered Nanoparticles ◽  
Mediation Effect ◽  
Global Index ◽  
Endothelial Cell Activation

Abstract Background Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. Results The average elemental carbon level inside carbon black bagging facilities was 657.0 μg/m3, which was 164-fold higher than that seen in reference areas (4.0 μg/m3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1β, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. Conclusions Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.

scholarly journals Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria

2020 ◽  
Vol 14 (7) ◽  
pp. e0007656
Author(s):  
João Conrado Khouri Dos-Santos ◽  
João Luiz Silva-Filho ◽  
Carla C. Judice ◽  
Ana Carolina Andrade Vitor Kayano ◽  
Júlio Aliberti ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Plasmodium Vivax Malaria

scholarly journals Signs of sympathetic and endothelial cell activation in the skin of patients with restless legs syndrome

2021 ◽  
Author(s):  
Melanie Bergmann ◽  
Anna Heidbreder ◽  
Ambra Stefani ◽  
Cecilia Raccagni ◽  
Elisabeth Brandauer ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Restless Legs Syndrome ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Restless Legs

OR17 Heme oxygenase-1 modulates HLA class I antibody-dependent endothelial cell activation

2015 ◽  
Vol 76 ◽  
pp. 15
Author(s):  
Eva Zilian ◽  
Hendry Saragih ◽  
Oliver Hiller ◽  
Abid Aljabri ◽  
Constanca Figueiredo ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Heme Oxygenase ◽  
Cell Activation ◽  
Hla Class I ◽  
Class I ◽  
Heme Oxygenase 1 ◽  
Endothelial Cell Activation

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

scholarly journals Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2520-2526 ◽  
Author(s):  
SJ van Deventer ◽  
HR Buller ◽  
JW ten Cate ◽  
LA Aarden ◽  
CE Hack ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Cell Activation ◽  
Plasminogen Activator Inhibitor ◽  
Contact System ◽  
Initial Increase ◽  
Cytokine Release ◽  
Endothelial Cell Activation ◽  
System A ◽  
Von Willebrand

Abstract Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.

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