VASCULAR BIOLOGY NAADP links histamine H1 receptors to secretion of von Willebrand factor in human endothelial cells

نویسندگان

  • Bianca Esposito
  • Guido Gambara
  • Alexander M. Lewis
  • Fioretta Palombi
  • Alessio D’Alessio
  • Lewis X. Taylor
  • Armando A. Genazzani
  • Elio Ziparo
  • Antony Galione
  • Grant C. Churchill
  • Antonio Filippini
چکیده

1Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy; 2Department of Pharmacology, University of Oxford, Oxford, United Kingdom; and 3Department of Chemical, Food, Pharmaceutical and Pharmacological Sciences and Drug and Food Biotechnology Center, Università del Piemonte Orientale, Novara, Italy

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NAADP links histamine H1 receptors to secretion of von Willebrand factor in human endothelial cells.

A variety of endothelial agonist-induced responses are mediated by rises in intracellular Ca(2+), suggesting that different Ca(2+) signatures could fine-tune specific inflammatory and thrombotic activities. In search of new intracellular mechanisms modulating endothelial effector functions, we identified nicotinic acid adenine dinucleotide phosphate (NAADP) as a crucial second messenger in hist...

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Endothelial cells regulate thrombosis, hemostasis, and inflammatory responses by supplying the vasculature with several factors that include procoagulant von Willebrand factor (VWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca2 regulated manner after endothelial activation but exhibit opposing physiologic effects. In search for factors that cou...

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Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor.

An elevated level of von Willebrand factor (VWF) in diabetic patients is associated with increased risk of thrombotic cardiovascular events. The underlying mechanism of how VWF expression is upregulated in diabetes mellitus is poorly understood. We now report that hyperglycemia-induced repression of microRNA-24 (miR-24) increases VWF expression and secretion in diabetes mellitus. In diabetic pa...

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Thrombin-mediated endothelial-cell release of von Willebrand factor (VWF) and P-selectin functionally links proteaseactivated receptors (PARs) to thrombosis and inflammation. VWF release can be stimulated by both Ca2 and cAMP, and, although both VWF and P-selectin are found in Weibel-Palade bodies (WPBs), we found that their release could be differentially regulated. In these studies, human umb...

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Small GTP-binding protein Ral is involved in cAMP-mediated release of von Willebrand factor from endothelial cells.

OBJECTIVE von Willebrand factor (vWF) is synthesized by endothelial cells and stored in specialized vesicles called Weibel-Palade bodies (WPBs). Recently, we have shown that the small GTP-binding protein Ral is involved in thrombin-induced exocytosis of WPBs. In addition to Ca2+-elevating secretagogues such as histamine and thrombin, release of WPB is also observed after administration of cAMP-...

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تاریخ انتشار 2011