Caruso Raffaele, Rocchiccioli Silvia, Gori Anna Maria, Cecchettini Antonella, Giusti Betti, Parodi Guido, Cozzi Lorena, Marcucci Rossella, Parolini Marina, Romagnuolo Ilaria, Citti Lorenzo, Abbate Rosanna, Parodi Oberdan
National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy.
Mediators Inflamm. 2015;2015:710123. doi: 10.1155/2015/710123. Epub 2015 Mar 19.
In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel.
Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined.
Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.
In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.
在急性冠状动脉综合征（ACS）中，炎症和氧化还原反应与氯吡格雷治疗时残余血小板反应性（RPR）增加有关。我们调查了氯吡格雷相互作用是否会影响血小板功能，并对ACS患者中对氯吡格雷反应不同的炎症和氧化相关因子进行调节。
对29例接受双联（阿司匹林/氯吡格雷）抗血小板治疗的ACS患者测量血小板聚集情况。无反应者（NR）定义为ADP诱导的RPR≥70%。检测了几个炎症和氧化还原参数，并测定了血小板蛋白质组。
29例ACS患者中有8例（28%）对氯吡格雷无反应。在24小时时，NR组中Th2型细胞因子IL-4、IFNγ和MCP-1水平较高，而NR组的血液谷胱甘肽（r-GSHbl）水平低于反应者（R）。蛋白质组学分析表明血小板粘附分子CD226水平上调，抗氧化剂过氧化物酶4下调。在R组患者中，促炎细胞因子IL-6减少，而抗炎细胞因子IL-1Ra增加。
在接受氯吡格雷治疗且RPR较高的患者中，急性期观察到炎症因子、血小板粘附分子以及循环和血小板抗氧化分子失衡。急性事件后，无反应者中促炎环境长期持续存在，而血液抗氧化因子倾向于恢复正常反应性。
