Abstract：
BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.
OBJECTIVE: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors.
RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
OBJECTIVE: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors.
RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
摘要：
背景：与氯吡格雷相比，血小板P2Y12拮抗剂替格瑞洛可降低急性心肌梗死（AMI）后的心血管死亡率，但潜在的机制是未知的。因为活化的血小板释放促动脉粥样硬化和促炎的microRNAs，包括miR-125a,miR-125b和miR-223，我们假设这些miRNA的表达在替格瑞洛上较低，与氯吡格雷相比。
目的：我们比较了miR-125a，接受替格瑞洛或氯吡格雷治疗的AMI患者血浆中miR-125b和miR-223的表达。
方法：乙酰水杨酸和氯吡格雷经皮冠状动脉介入治疗后，60例首次AMI患者随机转用替格瑞洛或继续服用氯吡格雷。miR-223、miR-125a-5p的血浆表达,在基线时、替格瑞洛或氯吡格雷治疗72小时和6个月后以及30名健康志愿者中的1人使用定量聚合酶链反应检测miR-125b。使用ADP测试的多电极聚集测定法用于确定响应于P2Y12抑制剂的血小板反应性。
结果：miR-125b在AMI患者72h和6个月中的表达更高，与健康志愿者相比（p=0.001），而miR-125a-5p和miR-223的表达具有可比性。在随机接受替格瑞洛治疗的患者中，miR-125b的表达在72h时降低(p=0.007),在6个月时升高回到基线(p=0.005)。miR-125a-5p和miR-223的表达不受从氯吡格雷转换为替格瑞洛的影响。
结论：替格瑞洛治疗导致AMI后血浆miR-125b表达降低，与氯吡格雷相比。较高的miR-125b表达可能解释了氯吡格雷治疗患者的复发性血栓事件和较差的临床结果。与替格瑞洛相比。
目的：我们比较了miR-125a，接受替格瑞洛或氯吡格雷治疗的AMI患者血浆中miR-125b和miR-223的表达。
方法：乙酰水杨酸和氯吡格雷经皮冠状动脉介入治疗后，60例首次AMI患者随机转用替格瑞洛或继续服用氯吡格雷。miR-223、miR-125a-5p的血浆表达,在基线时、替格瑞洛或氯吡格雷治疗72小时和6个月后以及30名健康志愿者中的1人使用定量聚合酶链反应检测miR-125b。使用ADP测试的多电极聚集测定法用于确定响应于P2Y12抑制剂的血小板反应性。
结果：miR-125b在AMI患者72h和6个月中的表达更高，与健康志愿者相比（p=0.001），而miR-125a-5p和miR-223的表达具有可比性。在随机接受替格瑞洛治疗的患者中，miR-125b的表达在72h时降低(p=0.007),在6个月时升高回到基线(p=0.005)。miR-125a-5p和miR-223的表达不受从氯吡格雷转换为替格瑞洛的影响。
结论：替格瑞洛治疗导致AMI后血浆miR-125b表达降低，与氯吡格雷相比。较高的miR-125b表达可能解释了氯吡格雷治疗患者的复发性血栓事件和较差的临床结果。与替格瑞洛相比。
