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Cardioprotective effects of dronedarone mediated by the influence on the expression of urokinase-type plasminogen activator receptor

Purpose: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone. Methods: Follow...

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Main Authors: Becher, Tobias (Author) , Seiler, Lea (Author) , Rudic, Boris (Author) , Röger, Susanne (Author) , Tueluemen, Erol (Author) , Liebe, Volker (Author) , Kuschyk, Jürgen (Author) , Trinkmann, Frederik (Author) , Michels-Zetsche, Julia D. (Author) , Weiß, Christel (Author) , Akın, Ibrahim (Author) , Kälsch, Thorsten (Author) , Borggrefe, Martin (Author) , Stach-Jablonski, Ksenija (Author)
Format: Article (Journal)
Language:English
Published: June 2019
In: Journal of vascular research
Year: 2019, Volume: 56, Issue: 2, Pages: 92-96
ISSN:1423-0135
DOI:10.1159/000499526
Online Access:Resolving-System, Volltext: http://doi.org/10.1159/000499526
Verlag, Volltext: https://www.karger.com/Article/Abstract/499526
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Author Notes:Tobias Becher, Lea Seiler, Boris Rudic, Susanne Roeger, Erol Tueluemen, Volker Liebe, Juergen Kuschyka, Frederik Trinkmann, Julia Michels, Christel Weiss, Ibrahim Akina, Thorsten Kaelsch, Martin Borggrefe, Ksenija Stach
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Summary:Purpose: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone. Methods: Following a 24-h incubation of human umbilical vein endothelial cells (HUVECs) with dronedarone (concentration 50, 100, and 150 ng/mL), they were then stimulated for 1 h with lipopolysaccharide (LPS) and were subsequently incubated in direct contact with thrombin-activated platelets. After incubation, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, urokinase-type plasminogen activator receptor (uPAR), and membrane type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. Results: Preincubation with 150 ng/mL of dronedarone reduced the expression of uPAR on endothelial cells after proinflammatory stimulation with LPS and also by direct endothelial contact with activated platelets (p = 0.0038). In contrast, the expression of CD40L and CD62P on platelets after proinflammatory stimulation with thrombin was significantly increased through direct preincubation with 50/100/150 ng/mL of dronedarone. However, dronedarone had no effects on the expression of MT1-MMP and ICAM-1 in HUVECs. Conclusion: In this in vitro analysis, dronedarone directly increased platelet activation but showed significant direct effects on endothelial cells and indirect effects on platelets on selected markers of atherosclerosis.
Item Description:Gesehen am 18.11.2019
Physical Description:Online Resource
ISSN:1423-0135
DOI:10.1159/000499526

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