Second Department of Cardiology, Jagiellonian University Medical College, Cracow, Poland.
Małopolska Center of Biotechnology, Jagiellonian University, Cracow, Poland.
Int J Med Sci. 2019 Jan 1;16(2):264-275. doi: 10.7150/ijms.28580. eCollection 2019.
: Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y adenosine diphosphate (ADP) receptor antagonists. In pre-discharge men treated with DAPT for an acute coronary syndrome, plasma PMVs were quantified by flow cytometry on the basis of CD62P (P-selectin) and CD42 (glycoprotein Ib) positivity, putative indices of PMVs release from activated and all platelets, respectively. ADP-induced platelet aggregation was measured by multiple-electrode aggregometry. Clinical characteristics were similar in patients on clopidogrel (n=16), prasugrel (n=10) and ticagrelor (n=12). Platelet reactivity was comparably reduced on ticagrelor or prasugrel versus clopidogrel (p<0.01). Compared to clopidogrel-treated patients, CD42/CD62P PMVs counts were 3-4-fold lower in subjects receiving ticagrelor (p=0.001) or prasugrel (p<0.05), while CD42 PMVs were significantly reduced on ticagrelor (by about 6-fold, p<0.001), but not prasugrel (p=0.3). CD42/CD62P PMVs numbers correlated positively to the ADP-induced aggregation on clopidogrel (p<0.01) or prasugrel (p<0.05), which was absent in ticagrelor users (p=0.8). CD42 PMVs counts were unrelated to platelet reactivity (p>0.5). Higher antiplatelet potency of prasugrel and ticagrelor versus clopidogrel is associated with decreased plasma CD42/CD62P PMVs numbers. However, in contrast to thienopyridines, the association of reduced CD42/CD62P PMVs counts with ticagrelor use appears independent of its anti-aggregatory effect. Despite similar platelet-inhibitory activity of ticagrelor and prasugrel, only the treatment with ticagrelor seems associated with lower total PMVs release. Our preliminary findings may suggest a novel pleiotropic effect of ticagrelor extending beyond pure anti-aggregatory properties of the drug.
血小板衍生的微泡（PMVs），从血小板表面膜脱落，构成了循环微泡的大部分，并与促凝、促炎和动脉粥样硬化前作用有关。我们的目的是比较在使用不同 P2Y 腺苷二磷酸（ADP）受体拮抗剂进行双重抗血小板治疗（DAPT）期间，与血小板反应性相关的血浆 PMVs 数量。在因急性冠状动脉综合征而接受 DAPT 治疗的出院前男性中，通过流式细胞术基于 CD62P（P-选择素）和 CD42（糖蛋白 Ib）阳性来定量检测血浆 PMVs，分别是激活和所有血小板释放 PMVs 的假定指标。通过多电极聚集仪测量 ADP 诱导的血小板聚集。在接受氯吡格雷（n=16）、普拉格雷（n=10）和替格瑞洛（n=12）治疗的患者中，临床特征相似。与氯吡格雷相比，替格瑞洛或普拉格雷可更显著地降低血小板反应性（p<0.01）。与接受氯吡格雷治疗的患者相比，接受替格瑞洛（p=0.001）或普拉格雷（p<0.05）治疗的患者 CD42/CD62P PMVs 计数低 3-4 倍，而替格瑞洛显著降低 CD42 PMVs（约 6 倍，p<0.001），但普拉格雷无此变化（p=0.3）。CD42/CD62P PMVs 数量与氯吡格雷（p<0.01）或普拉格雷（p<0.05）诱导的聚集呈正相关，而在替格瑞洛使用者中不存在这种相关性（p=0.8）。CD42 PMVs 计数与血小板反应性无关（p>0.5）。与氯吡格雷相比，普拉格雷和替格瑞洛的抗血小板作用更强，与血浆 CD42/CD62P PMVs 数量减少有关。然而，与噻吩吡啶类药物不同，与替格瑞洛使用相关的降低 CD42/CD62P PMVs 计数的关联似乎与其抗聚集作用无关。尽管替格瑞洛和普拉格雷的血小板抑制活性相似，但只有替格瑞洛治疗与更低的总 PMVs 释放有关。我们的初步发现可能表明替格瑞洛具有一种新的多效性作用，超出了药物的单纯抗聚集作用。
