Key result
Dronedarone (150 ng/mL) reduced the expression of uPAR on endothelial cells after proinflammatory stimulation (p=0.0038), while increasing platelet activation markers.
Why the study?
Observational data hypothesized a cardioprotective effect for dronedarone, prompting evaluation of its molecular atheroprotective effects in an in vitro endothelial cell-platelet model.
Dronedarone demonstrated mixed effects in an in vitro model, reducing endothelial uPAR expression but increasing platelet activation markers.
Mixed in vitro effects should not change dronedarone use; leaves open net vascular actions.
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.
No takes yet. Share an insight, caveat, or question.
Becher et al. (2019) studied Atherosclerosis. Dronedarone was evaluated on Expression of uPAR on endothelial cells (p=0.0038). Dronedarone (150 ng/mL) reduced the expression of uPAR on endothelial cells after proinflammatory stimulation (p=0.0038), while increasing platelet activation markers.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: