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

Cells

卷:8

GalinaYu. Mironova¹  AlexandraA. Tsitrina¹  PavelV. Avdonin¹  ElenaYu. Rybakova¹  PiotrP. Avdonin¹  SergeiK. Trufanov¹  NikolayV. Goncharov² 

[1] Koltsov Institute of Developmental Biology, Moscow 119334, Russia;

[2] Sechenov Institute of Evolutional Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg 194223, Russia;

关键词: histamine;    calcium;    endothelial cells;    NADPH-oxidase;    VAS2870;    von Willebrand factor;    aorta;    relaxation;   

DOI  :  10.3390/cells8020196

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown