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Differential Osteoprotegerin Kinetics after Stimulation with Desmopressin and Lipopolysaccharides In Vivo.

Abstract：

:Osteoprotegerin (OPG) regulates bone metabolism by reducing the activation of osteoclasts, but may also be involved in blood vessel calcification and atherosclerosis. Within endothelial cells OPG is stored in Weibel-Palade bodies (WPBs). Blood kinetics of OPG are essentially unknown. We aimed to assess these using two distinct in vivo models; one after stimulation with desmopressin (DDAVP) and another after stimulation with lipopolysaccharide (LPS). Both clinical trials were conducted at the Department of Clinical Pharmacology at the Medical University of Vienna, Austria. Participants received desmopressin (0.3 µg/kg), LPS (2 ng/kg), or placebo (sodium chloride 0.9%) with subsequent blood sampling at time points up to 24 hours after administration. The primary objective of this study was to investigate the plasma kinetics of OPG after stimulation with desmopressin and LPS. Secondary analyses included the release of other WPB contents including von Willebrand factor (vWF). This analysis included 31 healthy volunteers (n = 16 for desmopressin and placebo, n = 15 for LPS). Infusion of desmopressin did not increase OPG concentrations compared with placebo, while LPS infusion significantly increased OPG levels, both compared with desmopressin (p < 0.0001) and to placebo (p = 0.004), with a maximum of ∼twofold increase in OPG levels ∼6 hours after infusion. von Willebrand factor levels increased after both desmopressin and LPS infusion (p < 0.0001), with a maximum of ∼threefold increase 2 hours after desmopressin and a maximum of ∼twofold increase 6 hours after LPS administration. In conclusion, we report that, in contrast to vWF, OPG is not released upon stimulation with desmopressin, but increases significantly during experimental endotoxemia.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Buchtele N,Kovacevic KD,Brostjan C,Schwameis M,Hayden H,Derhaschnig U,Firbas C,Jilma B,Schoergenhofer C

doi

10.1055/s-0040-1712448

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

1108-1115

issue

7

eissn

0340-6245

issn

2567-689X

journal_volume

120

pub_type

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