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: | , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 2019
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| 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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| 245 | 1 | 0 | |a Cardioprotective effects of dronedarone mediated by the influence on the expression of urokinase-type plasminogen activator receptor |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Atrial fibrillation | |
| 650 | 4 | |a atrial-fibrillation | |
| 650 | 4 | |a Dronedarone | |
| 650 | 4 | |a Endothelial cells | |
| 650 | 4 | |a heart | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a platelets | |
| 650 | 4 | |a Platelets | |
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