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Thromb Haemost 2020; 120(07): 1108-1115
DOI: 10.1055/s-0040-1712448
Endothelium and Angiogenesis
Georg Thieme Verlag KG Stuttgart · New York

Differential Osteoprotegerin Kinetics after Stimulation with Desmopressin and Lipopolysaccharides In Vivo

Nina Buchtele
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
2   Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Katarina D. Kovacevic
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Christine Brostjan 
3   Department of Surgery, Medical University of Vienna, Vienna, Austria
,
Michael Schwameis
4   Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
,
Hubert Hayden
3   Department of Surgery, Medical University of Vienna, Vienna, Austria
,
Ulla Derhaschnig
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Christa Firbas
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Bernd Jilma
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Christian Schoergenhofer
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
› Institutsangaben Funding This study was funded by the Austrian Science Fund FWF grant SFB54–04/APF05404FW.
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Publikationsverlauf

24. Februar 2020

18. April 2020

Publikationsdatum:
29. Mai 2020 (online)

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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.

Keywords

osteoprotegerin - Weibel–Palade bodies - secretion/exocytosis - endothelial cells

Authors' Contributions

Conceptualization: N.B., C.S., and B.J.; Data curation: N.B., U.D., C.F., and C.S.; Formal analysis: C.S., B.J., and M.S.; Funding acquisition: B.J.; Methodology: K.K., C.B., H.H., and M.S.; Project administration: N.B., C.S.; Supervision: B.J.; Writing – original draft: N.B. and C.S.; Writing – review and editing: K.K., C.B., M.S., H.H., U.D., C.F., and B.J.


Supplementary Material

 

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