Resolvin E1 regulates adenosine diphosphate activation of human platelets.
Resolvin E1 regulates adenosine diphosphate activation of human platelets.
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DOI：
10.1161/atvbaha.110.209908
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Serhan CN
中科院分区：
文献类型：
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作者：
Fredman G;Van Dyke TE;Serhan CN
Resolvin E1 （RvE1）是一种由二十碳五烯酸（EPA）衍生的，在急性炎症消退过程中产生的特殊促消退介质。RvE1在体内表现出强大的器官保护作用，并对包括血小板在内的特定细胞类型起作用。在这里，我们研究了RvE1通过特定受体调节血小板二磷酸腺苷（ADP）激活的能力，因为RvE1通过某些激动剂（包括ADP）减少血小板聚集。与血小板孵育的RvE1 （0.1nM-100nM）与对照血小板相比，adp刺激的p -选择素动员（IC50 ~1.6×10−12 M）和聚合肌动蛋白含量降低。RvE1 （1-100nM）不刺激或阻断细胞内钙动员。使用新的P2Y12-β-抑制蛋白偶联细胞系统，adp激活的P2Y12 EC50为5×10−6 M， RvE1不直接刺激P2Y12或阻断ADP-P2Y12信号。在该系统中，另一种二十烷类LTE4 （EC50 1.3×10−11 M）剂量依赖性地激活P2Y12。将表达p2y12的重组细胞瞬时转染RvE1受体人ChemR23（存在于人血小板上），与模拟转染相比，RvE1 （0.1nM-10.0nM）阻断了表达p2y12 -ChemR23的细胞中的ADP信号（IC50 ~1.6×10−11 M）。这些结果表明，RvE1的调控作用（即减少adp刺激的p -选择素动员和肌动蛋白聚合）依赖于hchemr23。此外，他们记录了RvE1选择性参与adp活化血小板的特异性血小板作用，阐明了一种新的细胞机制和omega-3 EPA的影响，可能有助于血管炎症的解决和与病理性心血管事件相关的adp依赖性血小板活化。
Resolvin E1 (RvE1) is an eicosapentaenoic acid (EPA)-derived specialized pro-resolving mediator generated during resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types including platelets. Here, we investigated the ability of RvE1 to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists including ADP. RvE1 (0.1nM–100nM) incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC50 ~1.6×10−12 M) and polymerized actin content compared to control platelets. RvE1 (1–100nM) did not stimulate or block intracellular calcium mobilization. Using a new P2Y12-β-arrestin-coupled cell system, ADP-activated P2Y12 with an EC50 of 5×10−6 M and RvE1 did not directly stimulate P2Y12 or block ADP-P2Y12 signals. In this system, another eicosanoid LTE4 (EC50 1.3×10−11 M) dose dependently activated P2Y12. When recombinant P2Y12-expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), addition of RvE1 (0.1nM-10.0nM) blocked ADP signals (IC50 ~1.6×10−11 M) in P2Y12-ChemR23-expressing cells compared to mock transfections. These results demonstrate that RvE1’s regulatory actions (i.e reducing ADP-stimulated P-selectin mobilization and actin polymerization) are hChemR23-dependent. Moreover, they document specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and impact of omega-3 EPA that may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathologic cardiovascular events.