scholarly journals VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 196 ◽  
Author(s):  
Pavel Avdonin ◽  
Elena Rybakova ◽  
Piotr Avdonin ◽  
Sergei Trufanov ◽  
Galina Mironova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Calcium Concentration ◽  
Umbilical Vein ◽  
Rat Aorta ◽  
Human Umbilical Vein ◽  
Nox Inhibitors ◽  
Umbilical Vein Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

In this study, we investigated the effects of NAD(P)H oxidase (NOX) inhibitor VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine) on the histamine-induced elevation of free cytoplasmic calcium concentration ([Ca2+]i) and the secretion of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs) and on relaxation of rat aorta in response to histamine. At 10 μM concentration, VAS2870 suppressed the [Ca2+]i rise induced by histamine. Inhibition was not competitive, with IC50 3.64 and 3.22 μM at 1 and 100 μM concentrations of histamine, respectively. There was no inhibition of [Ca2+]i elevation by VAS2870 in HUVECs in response to the agonist of type 1 protease-activated receptor SFLLRN. VAS2870 attenuated histamine-induced secretion of vWF and did not inhibit basal secretion. VAS2870 did not change the degree of histamine-induced relaxation of rat aortic rings constricted by norepinephrine. We suggest that NOX inhibitors might be used as a tool for preventing thrombosis induced by histamine release from mast cells without affecting vasorelaxation.

Hydrogen peroxide stimulates exocytosis of von Willebrand factor in human umbilical vein endothelial cells

2017 ◽  
Vol 44 (5) ◽  
pp. 531-537 ◽  
Author(s):  
P. V. Avdonin ◽  
A. A. Tsitrina ◽  
G. Y. Mironova ◽  
P. P. Avdonin ◽  
I. L. Zharkikh ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Protein tyrosine kinases regulate agonist-stimulated prostacyclin release but not von Willebrand factor secretion from human umbilical vein endothelial cells

1996 ◽  
Vol 315 (2) ◽  
pp. 407-416 ◽  
Author(s):  
Caroline P. D. WHEELER-JONES ◽  
Michael J. MAY ◽  
Anthony J. MORGAN ◽  
Jeremy D. PEARSON
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Phosphorylation ◽  
Von Willebrand Factor ◽  
Tyrosine Kinases ◽  
Umbilical Vein ◽  
Protein Tyrosine Kinases ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

The rapid synthesis and release of prostacyclin (PGI2) and the exocytotic secretion of von Willebrand Factor (vWF) elicited by activation of G-protein-coupled receptors on endothelium occur via signalling mechanisms which are incompletely defined. Activation of protein tyrosine kinases (PTKs) and modulation of the tyrosine-phosphorylation state of endogenous proteins have been implicated in several cellular processes including arachidonate release and exocytosis. In the present study we have examined the regulatory role of PTKs in agonist-stimulated release of PGI2 and vWF from human umbilical vein endothelial cells (HUVECs) using two chemically and mechanistically dissimilar PTK inhibitors (genistein and ST271). Genistein, but not the less active analogue daidzein, dose-dependently attenuated PGI2 release in response to thrombin and histamine (IC50 approx. 20 μM), and to the thrombin-receptor-activating peptide. A more potent inhibition of thrombin- and histamine-induced PGI2 synthesis was observed in cells exposed to ST271. In contrast, neither genistein nor ST271 modulated agonist-drive vWF secretion. At concentrations that abolished PGI2 release, genistein blocked thrombin- or histamine-evoked tyrosine phosphorylation of a 42 kDa protein. Ca2+ ionophore-induced PGI2 generation, but not vWF secretion, was also inhibited by both genistein and ST271, suggesting that these agents modulate PGI2 synthesis by acting at, or distal to, agonist-induced changes in intracellular Ca2+ ([Ca2+]i). In fura-2-loaded HUVECs genistein partially reduced the histamine-induced peak [Ca2+]i but had no effect on the thrombin response. Ca2+-induced PGI2 release from electrically permeabilized HUVECs was abolished in the presence of ST271 or genistein, but not daidzein. The generation of PGI2 in response to exogenous arachidonic acid was not modulated by genistein or ST271, suggesting that PTK inhibitors do not directly inhibit cyclo-oxygenase activity. Taken together, these results suggest that PTKs regulate PGI2 synthesis and release in HUVECs by modulating, directly or indirectly, a Ca2+-sensitive step upstream of cyclo-oxygenase.

Factor VIIa Induced Release of von Willebrand Factor from Human Umbilical Vein Endothelial Cells by a Tyrosine Kinase Dependent Pathway

2002 ◽  
Vol 87 (06) ◽  
pp. 1057-1061 ◽  
Author(s):  
Derrick Bowen ◽  
Maurice Hallett ◽  
John Giddings ◽  
Peter Collins ◽  
Simon Brown
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Von Willebrand Factor ◽  
Kinase Inhibitor ◽  
Factor Viia ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe interaction of FVIIa with surface-bound tissue factor (TF) induces various cellular changes including cytosolic Ca2+ signals. The release of von Willebrand factor (VWF) from endothelial cell stores may be triggered by an elevation in cytosolic free Ca2+, therefore we investigated the effect of rFVIIa on the release of VWF from human umbilical vein endothelial cells (HUVEC). We show here that rFVIIa induces the release of VWF from HUVEC with or without prestimulation with lipopolysaccharide (LPS). The effect of rFVIIa was dose dependent. However, the release of VWF by HUVEC in response to rFVIIa was significantly greater with LPS prestimulation (3.18 times control) than without LPS prestimulation (1.45 times control) (p <0.001). Cytosolic Ca2+ signals were detectable only after LPS prestimulation of HUVEC and these were small compared to those elicited by thrombin. No effect on rFVIIa induced release of VWF was seen in the presence of hirudin, site inactivated rFVIIa or the protein kinase C (PKC) inhibitor staurosporine. However, a tyrosine kinase inhibitor genistein, inhibited the rFVIIa induced release of VWF. These data show that release of VWF can occur without involvement of the cytosolic Ca2+/ PKC pathway. FVIIa induced VWF release from endothelial cells may have in vivo significance at sites of TF expression.

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