Resolvin E1 Regulates Adenosine Diphosphate Activation of Human Platelets
- 1 October 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 30 (10), 2005-2013
- https://doi.org/10.1161/atvbaha.110.209908
Abstract
Objective— To investigate the ability of resolvin E1 (RvE1) to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists, including ADP. Methods and Results— RvE1 is an eicosapentaenoic acid–derived specialized proresolving mediator generated during the resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types, including platelets. RvE1, 0.1 to 100 nmol/L, incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC 50 , approximately 1.6×10 −12 mol/L) and polymerized actin content compared with control platelets. RvE1, 1 to 100 nmol/L, did not stimulate or block intracellular Ca 2+ mobilization. By using a new P2Y 12 –β-arrestin–coupled cell system, ADP-activated P2Y 12 with an EC 50 of 5×10 −6 mol/L and RvE1 did not directly stimulate P2Y 12 or block the ADP–P2Y 12 signals. In this system, another eicosanoid, leukotriene E 4 (LTE 4 ) (EC 50 , 1.3×10 −11 mol/L), dose dependently activated P2Y 12 . When recombinant P2Y 12 –expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), with the addition of RvE1 (0.1–10.0 nmol/L), blocked ADP signals (IC 50 , approximately 1.6×10 −11 mol/L) in P2Y 12 –ChemR23–expressing cells compared with mock transfections. Conclusion— RvE1’s regulatory actions (ie, reducing ADP-stimulated P-selectin mobilization and actin polymerization) are human (h)ChemR23-dependent. Moreover, specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and affect ω-3 eicosapentaenoic acid, which may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathological cardiovascular events.Keywords
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