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

Авдонин, П. В.; Tsitrina, Alexandra A.; Mironova, Galina Yu; Avdonin, P. P.; Zharkikh, Irina; Nadeev, A. D.; Гончаров, Н. В.

doi:10.1134/s106235901705003x

Cited by 6 publications

(9 citation statements)

References 30 publications

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“…We then studied endothelial phenotype with noncytotoxic concentrations of H 2 O 2 and found that several hours after exposure to H 2 O 2 , carbachol, or PMA, intracellular VWF level decreased, apparently due to exocytosis of WPB content [19]. This was confirmed by analysis of immunofluorescence microscopy data: H 2 O 2 at a nontoxic concentration (100 μM) increased the amount of VWF secreted by HUVECs by 43% over control and elevated total exposition of VWF on cell surface up to 94% [147]. PMA determines the progressive increase in expression of ACE (CD143), by 42 and 180% after 3 and 24 hours, respectively, whereas under the action of H 2 O 2 , ACE expression increases slowly and insignificantly (maximally by 34% after 24 hours of 200 μM H 2 O 2 application).…”

Section: Ros and Other Modulators Of The State Of Endotheliummentioning

confidence: 68%

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

Гончаров

Nadeev

Jenkins

et al. 2017

Oxidative Medicine and Cellular Longevity

167

115

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Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.

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Section: Ros and Other Modulators Of The State Of Endotheliummentioning

confidence: 68%

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

Гончаров

Nadeev

Jenkins

et al. 2017

Oxidative Medicine and Cellular Longevity

167

115

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“…Moreover, EC functioning is affected by the exogenous H 2 O 2 secreted by neu trophils. We have shown previously that exogenously added H 2 O 2 penetrates into ECs [26]. H 2 O 2 acts as a sec ond messenger by inhibiting protein tyrosine phos phatases [37].…”

Section: Resultsmentioning

confidence: 94%

“…The number of the cells in the 1.5 × 2 mm area was 2800 3000. The images were analyzed with the open access CellProfiler program (http://cellprofiler.org/releases) [25] (detailed description of the application of this pro gram for the analysis of images of ECs was published in [26]). The total number of analyzed frames was 96 128 (16 frames for each well in a 48 well plate).…”

Section: Methodsmentioning

confidence: 99%

The Use of Fluorescently Labeled ARC1779 Aptamer for Assessing the Effect of H2O2 on von Willebrand Factor Exocytosis

Avdonin

Trufanov

Rybakova

et al. 2020

Biochemistry Moscow

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Here, we propose a new approach for quantitative estimation of von Willebrand factor (vWF) exposed on the surface of endothelial cells (ECs) using the ARC1779 aptamer that interacts with the vWF A1 domain. To visualize complex formation between vWF and the aptamer, the latter was conjugated with the Cy5 fluorescent label. Cultured human umbilical vein endothelial cells (HUVEC) were stained with the ARC1779-Cy5 conjugate and imaged with a fluorescence microscope. The images were analyzed with the CellProfiler software. vWF released from the Weibel–Palade bodies was observed as bright dot-like structures of round and irregular shape, the number of which increased several times after HUVEC exposure to histamine or thrombin. Staining with ARC1779-Cy5 also revealed long filamentous vWF structures on the surface of activated HUVEC. vWF secretion by ECs is activated by the second messengers cAMP and Ca2+. There is evidence that hydrogen peroxide also acts as a second messenger in ECs. In addition, exogenous H2O2 formed in leukocytes can enter ECs. The aim of our study was to determine the effect of H2O2 on the vWF exposure at the surface of HUVEC using the proposed method. It was shown that hydrogen peroxide at concentration 100 µM, which is lower than the cytotoxicity threshold of H2O2 for cultured HUVEC, increased several times the number of dot-like structures and total amount of vWF exposed on plasma membrane of HUVEC, which suggest that H2O2 acts as a mediator that activates exocytosis of Weibel–Palade bodies and vWF secretion in the vascular endothelium during inflammation and upon elevated generation of endogenous reactive oxygen species in ECs.

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“…Direct activation of vWF secretion was demonstrated for superoxide anion [30]. We have recently shown that H 2 O 2 induces the exocytosis of vWF in HUVECs [35]. The physiological significance of the stimulation of vWF exocytosis and secretion by ROS is not clear.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we demonstrated an involvement of two-pore channels in an H 2 O 2 -induced increase in the level of calcium ions in the cytoplasm of human umbilical vein endothelial cells (HUVECs) [34]. This could be coupled with exocytosis of the von Willebrand factor (vWF) in these cells in response to H 2 O 2 [35]. The vWF release from EC is induced by superoxide anion [30].…”

Section: Introductionmentioning

confidence: 99%

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

Авдонин

Rybakova

Avdonin

et al. 2019

Cells

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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.

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

Cited by 6 publications

References 30 publications

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

The Use of Fluorescently Labeled ARC1779 Aptamer for Assessing the Effect of H2O2 on von Willebrand Factor Exocytosis

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

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