VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells
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 ([Ca<sup>2+</sup>]<sub>i</sub>) and the secreti...
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doaj-3f70f47e463d4e6094624e33ce9f50202020-11-24T20:40:18ZengMDPI AGCells2073-44092019-02-018219610.3390/cells8020196cells8020196VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial CellsPavel V. Avdonin0Elena Yu. Rybakova1Piotr P. Avdonin2Sergei K. Trufanov3Galina Yu. Mironova4Alexandra A. Tsitrina5Nikolay V. Goncharov6Koltsov Institute of Developmental Biology, Moscow 119334, RussiaKoltsov Institute of Developmental Biology, Moscow 119334, RussiaKoltsov Institute of Developmental Biology, Moscow 119334, RussiaKoltsov Institute of Developmental Biology, Moscow 119334, RussiaKoltsov Institute of Developmental Biology, Moscow 119334, RussiaKoltsov Institute of Developmental Biology, Moscow 119334, RussiaSechenov Institute of Evolutional Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg 194223, RussiaIn 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 ([Ca<sup>2+</sup>]<sub>i</sub>) 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 [Ca<sup>2+</sup>]<sub>i</sub> 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 [Ca<sup>2+</sup>]<sub>i</sub> 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.https://www.mdpi.com/2073-4409/8/2/196histaminecalciumendothelial cellsNADPH-oxidaseVAS2870von Willebrand factoraortarelaxation |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pavel V. Avdonin Elena Yu. Rybakova Piotr P. Avdonin Sergei K. Trufanov Galina Yu. Mironova Alexandra A. Tsitrina Nikolay V. Goncharov |
spellingShingle |
Pavel V. Avdonin Elena Yu. Rybakova Piotr P. Avdonin Sergei K. Trufanov Galina Yu. Mironova Alexandra A. Tsitrina Nikolay V. Goncharov VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells Cells histamine calcium endothelial cells NADPH-oxidase VAS2870 von Willebrand factor aorta relaxation |
author_facet |
Pavel V. Avdonin Elena Yu. Rybakova Piotr P. Avdonin Sergei K. Trufanov Galina Yu. Mironova Alexandra A. Tsitrina Nikolay V. Goncharov |
author_sort |
Pavel V. Avdonin |
title |
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells |
title_short |
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells |
title_full |
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells |
title_fullStr |
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells |
title_full_unstemmed |
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells |
title_sort |
vas2870 inhibits histamine-induced calcium signaling and vwf secretion in human umbilical vein endothelial cells |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-02-01 |
description |
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 ([Ca<sup>2+</sup>]<sub>i</sub>) 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 [Ca<sup>2+</sup>]<sub>i</sub> 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 [Ca<sup>2+</sup>]<sub>i</sub> 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. |
topic |
histamine calcium endothelial cells NADPH-oxidase VAS2870 von Willebrand factor aorta relaxation |
url |
https://www.mdpi.com/2073-4409/8/2/196 |
work_keys_str_mv |
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