scholarly journals Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells

2006 ◽  
Vol 7 (11) ◽  
pp. 899-905 ◽  
Author(s):  
Yi Li ◽  
Bin Du ◽  
Jia-qi Pan ◽  
De-chang Chen ◽  
Da-wei Liu
Keyword(s):  
Endothelial Cells ◽  
Interleukin 6 ◽  
Protein C ◽  
Umbilical Vein ◽  
Activated Protein C ◽  
Interleukin 8 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

scholarly journals Activated Protein C Induces Endoplasmic Reticulum Stress and Attenuates Lipopolysaccharide-Induced Apoptosis Mediated by Glycogen Synthase Kinase-3β

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Liang Luo ◽  
Tangfeng Lv ◽  
Qian Wang ◽  
Ting Zhang ◽  
Xiaoling Gu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein C ◽  
Glycogen Synthase ◽  
Umbilical Vein ◽  
Activated Protein C ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3βand inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.

scholarly journals Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-αStimulated Human Umbilical Vein Endothelial Cells

2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
Chaur-Jong Hu ◽  
Yueh-Lun Lee ◽  
Neng-Yao Shih ◽  
Yi-Yuan Yang ◽  
Suparat Charoenfuprasert ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Thrombus Formation ◽  
Umbilical Vein ◽  
Interleukin 8 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Human Umbilical Vein ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Treatment And Prevention ◽  
Umbilical Vein Endothelial Cells

Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-αstimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-αinduced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

Platelet factor 4 enhances generation of activated protein C in vitro and in vivo

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 146-151 ◽  
Author(s):  
Arne Slungaard ◽  
Jose A. Fernandez ◽  
John H. Griffin ◽  
Nigel S. Key ◽  
Janel R. Long ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein C ◽  
Umbilical Vein ◽  
Activated Protein C ◽  
Platelet Factor 4 ◽  
In Vivo Model ◽  
Platelet Factor ◽  
Umbilical Vein Endothelial Cells

Abstract Platelet factor 4 (PF4), an abundant platelet α-granule protein, accelerates in vitro generation of activated protein C (APC) by soluble thrombin/thrombomodulin (TM) complexes up to 25-fold. To test the hypothesis that PF4 similarly stimulates endothelium-associated TM, we assessed the influence of human PF4 on thrombin-dependent APC generation by cultured endothelial monolayers. APC generated in the presence of 1 to 100 μg PF4 was up to 5-fold higher than baseline for human umbilical vein endothelial cells, 10-fold higher for microvascular endothelial cells, and unaltered for blood outgrowth endothelial cells. In an in vivo model, cynomolgus monkeys (n = 6, each serving as its own control) were infused with either PF4 (7.5 mg/kg) or vehicle buffer, then with human thrombin (1.0 μg/kg/min) for 10 minutes. Circulating APC levels (baseline 3 ng/mL) peaked at 10 minutes, when PF4-treated and vehicle-treated animals had APC levels of 67 ± 5 ng/mL and 39 ± 2 ng/mL, respectively (P < .001). The activated partial thromboplastin time (APTT; baseline, 28 seconds) increased maximally by 27 ± 6 seconds in PF4-treated animals and by 9 ± 1 seconds in control animals at 30 minutes (P < .001). PF4-dependent increases in circulating APC and APTT persisted more than 2-fold greater than that of control's from 10 through 120 minutes (P ≤ .04). All APTT prolongations were essentially reversed by monoclonal antibody C3, which blocks APC activity. Thus, physiologically relevant concentrations of PF4 stimulate thrombin-dependent APC generation both in vitro by cultured endothelial cells and in vivo in a primate thrombin infusion model. These findings suggest that PF4 may play a previously unsuspected physiologic role in enhancing APC generation. (Blood. 2003;102:146-151)

The Suppression of the Coagulation of Nonanticoagulated Whole Blood in vitro by Human Umbilical Endothelial Cells Cultivated on Microcarriers is not Dependent on Protein C Activation

1995 ◽  
Vol 73 (04) ◽  
pp. 719-724 ◽  
Author(s):  
Hans-Peter Kohler ◽  
Michele Müller ◽  
Thomas Bombeli ◽  
P Werner Straub ◽  
André Haeberli
Keyword(s):  
Endothelial Cells ◽  
Whole Blood ◽  
Protein C ◽  
Umbilical Vein ◽  
Activated Protein C ◽  
Volume Ratio ◽  
Endothelial Cell Surface ◽  
Direct Measurements ◽  
Umbilical Vein Endothelial Cells

SummaryHuman umbilical vein endothelial cells (HUVEC) were cultivated on globular microcarriers in order to improve the endothelial cell surface to blood-volume ratio over the conventional flat bed cultures. HUVEC-beads were tested for their modulation of blood coagulation using a combination of two steps: HUVEC-beads were added into the syringe used for the venipuncture, in order to achieve immediate contact between cells and blood, and no anticoagulant was used during the incubation time of HUVEC-beads with whole blood. The coagulation initiation produced by venipuncture was almost completely suppressed as judged by thrombin measurements over a period of 60 min. The activated partial thromboplastin time showed a prolongation by a factor >3. Direct measurements of activated protein C (APC) were negative. Moreover, inhibition of APC-generation with a monoclonal anti-human protein C antibody did not affect the anticoagulant properties of endothelial cells. Therefore the anticoagulant properties exerted by HUVEC-beads are not dependent on APC.

scholarly journals Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3442-3451 ◽  
Author(s):  
Beatrice Saposnik ◽  
Elodie Lesteven ◽  
Anna Lokajczyk ◽  
Charles T. Esmon ◽  
Martine Aiach ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein C ◽  
Transmembrane Domain ◽  
Umbilical Vein ◽  
Expression Patterns ◽  
Soluble Form ◽  
Cell Protein ◽  
Human Umbilical Cord ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Abstract The endothelial cell protein C receptor also exists in soluble form in plasma (sEPCR), resulting from ADAM17 cleavage. Elevated sEPCR levels are observed in subjects carrying the A3 haplotype, which is characterized by a Ser219Gly substitution in the transmembrane domain, rendering the receptor more sensitive to cleavage. Because sEPCR production is not completely blocked by metalloprotease inhibition, we looked for another mechanism. Comparing mRNA expression patterns and levels in A3 and non-A3 cells from 32 human umbilical cord veins, we detected a truncated mRNA in addition to the full-length mRNA. This truncated mRNA was 16 times more abundant in A3 human umbilical vein endothelial cells than in non-A3 human umbilical vein endothelial cells and encoded a protein lacking the transmembrane domain. We stably expressed a recombinant form of this protein (rEPCRisoform) and a protein mimicking the plasma sEPCR (rEPCRsol). Functional studies of the purified recombinant proteins revealed that the rEPCRisoform bound to recombinant protein C with similar affinity than rEPCRsol and that it also inhibited the anticoagulant activity of APC. Trace amounts of the EPCR isoform were found in the plasma of A3 subjects. These results suggest that the sEPCRisoform could contribute to the regulatory effect of sEPCR in plasma.

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