Lannan K L, Spinelli S L, Blumberg N, Phipps R P
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
J Thromb Haemost. 2017 Apr;15(4):802-813. doi: 10.1111/jth.13620. Epub 2017 Feb 25.
Essentials Specialized proresolving mediators (SPMs) promote the resolution of inflammation. This study sought to investigate the effects of SPMs on human platelet function. The SPM, Maresin 1, enhanced hemostatic, but suppressed inflammatory functions of platelets. SPMs uniquely regulate platelet function and may represent a new class of antiplatelet agents.
Background Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side-effects, including increased risk of bleeding, and some patients are relatively 'aspirin-resistant'. Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation. Objectives A major unmet need in the field of hematology is the development of new agents that safely prevent unwanted platelet activation in patients with underlying cardiovascular disease, while minimizing the risk of bleeding. Here, we investigate the potential of endogenously produced, specialized pro-resolving mediators (SPMs) as novel antiplatelet agents. SPMs are a recently discovered class of lipid-derived molecules that drive the resolution of inflammation without being overtly immunosuppressive. Methods Human platelets were treated with lipoxin A4, resolvin D1, resolvin D2, 17-HDHA or maresin 1 for 15 min, then were subjected to platelet function tests, including spreading, aggregation and inflammatory mediator release. Results We show for the first time that human platelets express the SPM receptors, GPR32 and ALX. Furthermore, our data demonstrate that maresin 1 differentially regulates platelet hemostatic function by enhancing platelet aggregation and spreading, while suppressing release of proinflammatory and prothrombotic mediators. Conclusions These data support the concept that SPMs differentially regulate platelet function and may represent a novel class of antiplatelet agents. SPMs also may play an important role in the resolution of inflammation in cardiovascular diseases.
基本情况 专门的促炎症消退介质（SPMs）可促进炎症的消退。本研究旨在探究SPMs对人血小板功能的影响。SPM玛瑞新1增强了止血功能，但抑制了血小板的炎症功能。SPMs独特地调节血小板功能，可能代表一类新型抗血小板药物。
背景 抗血小板治疗是现代医学实践的基石，常用于降低心肌梗死、血栓形成和中风的可能性。然而，目前的抗血小板治疗，如阿司匹林，往往有不良副作用，包括出血风险增加，而且一些患者相对“阿司匹林抵抗”。血小板密切参与止血和炎症过程，临床后果与血小板过度或不足激活有关。目的 血液学领域一个尚未满足的主要需求是开发新药物，以安全地防止患有潜在心血管疾病的患者出现不必要的血小板激活，同时将出血风险降至最低。在此，我们研究内源性产生的专门促炎症消退介质（SPMs）作为新型抗血小板药物的潜力。SPMs是最近发现的一类脂质衍生分子，可驱动炎症的消退而无明显免疫抑制作用。方法 用人脂氧素A4、消退素D1、消退素D2、17-羟基二十二碳六烯酸或玛瑞新1处理人血小板15分钟，然后进行血小板功能测试，包括铺展、聚集和炎症介质释放。结果 我们首次表明人血小板表达SPM受体GPR32和ALX。此外，我们的数据表明玛瑞新1通过增强血小板聚集和铺展，同时抑制促炎和促血栓形成介质的释放，以不同方式调节血小板止血功能。结论 这些数据支持SPMs以不同方式调节血小板功能的概念，可能代表一类新型抗血小板药物。SPMs在心血管疾病炎症的消退中也可能起重要作用。
