替卡格雷抑制急性冠状动脉综合征中 Toll 样受体和蛋白酶激活受体介导的血小板激活。
Ticagrelor Inhibits Toll-Like and Protease-Activated Receptor Mediated Platelet Activation in Acute Coronary Syndromes.
机构信息
Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
出版信息
Cardiovasc Drugs Ther. 2020 Feb;34(1):53-63. doi: 10.1007/s10557-019-06932-7.
PURPOSE
Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS).
METHODS
Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry.
RESULTS
ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02).
CONCLUSION
Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
目的
替格瑞洛抑制细胞摄取腺苷，从而增加细胞外腺苷浓度和生物活性，我们假设替格瑞洛具有依赖于腺苷的抗血小板特性。在本研究中，我们比较了替格瑞洛和普拉格雷对急性冠脉综合征（ACS）患者血小板激活的影响。
方法
采用流式细胞术检测 80 例接受经皮冠状动脉介入治疗（PCI）后第 3 天的替格瑞洛和 80 例普拉格雷治疗的 ACS 患者血液中血小板表面 P-选择素和活化糖蛋白（GP）IIb/IIIa 对二磷酸腺苷（ADP）、Toll 样受体（TLR）-1/2 激动剂 Pam3CSK4、TLR-4 激动剂脂多糖（LPS）、蛋白酶激活受体（PAR）-1 激动剂 SFLLRN 和 PAR-4 激动剂 AYPGKF 的反应。采用多电极聚集仪和透光比浊法评估花生四烯酸（AA）和 ADP 诱导的残余血小板聚集。
结果
ADP 诱导的血小板激活和聚集以及 AA 诱导的血小板聚集在替格瑞洛和普拉格雷组患者中相似（均 p≥0.3）。此外，LPS 诱导的替格瑞洛和普拉格雷治疗患者血小板表面 P-选择素和活化 GPIIb/IIIa 的表达无显著差异（均 p>0.4）。相反，替格瑞洛治疗患者 Pam3CSK4 诱导的血小板表面 P-选择素和活化 GPIIb/IIIa 的表达显著低于普拉格雷治疗患者（均 p≤0.005）。此外，与接受普拉格雷治疗的患者相比，替格瑞洛治疗患者 SFLLRN 诱导的血小板表面 P-选择素和活化 GPIIb/IIIa 的表达明显降低（均 p<0.03）。最后，替格瑞洛治疗患者对 AYPGKF 刺激后通过血小板表面活化 GPIIb/IIIa 评估的 PAR-4 介导的血小板激活明显低于接受普拉格雷治疗的患者（p=0.02）。
结论
与普拉格雷相比，替格瑞洛在 ACS 患者中更能抑制 TLR-1/2 和 PAR 介导的血小板激活。
Zotero 插件