循环凋亡微粒在急性冠状动脉综合征中的作用

Effect of circulating apoptotic microparticles on acute coronary syndrome

目的:探讨凋亡微粒在急性冠状动脉综合征(ACS)中的作用。方法:前瞻性对照研究,入选2016年2月至2018年7月,在我院行冠状动脉造影的ACS患者122例,其中49例ST段抬高型心肌梗死(STEMI),35例非STEMI和38例不稳定型心绞痛。对照组为15例稳定型心绞痛患者和16例冠状动脉造影正常患者。在冠状动脉造影前采集静脉血,使用流式细胞仪定量分析内皮细胞来源(EMP)、红细胞来源(RMP)和血小板来源的微粒(PMP)。用膜联蛋白V染色检测凋亡和非凋亡微粒。用超声检测血流介导的肱动脉舒张功能(FMD)评估内皮功能。采用层次聚类并根据凋亡微粒水平对ACS患者进行分析。结果:ACS患者凋亡微粒水平明显升高(各组间比较,凋亡EMP P<0.0001,凋亡RMP P=0.002,PMP P=0.01)。而各组间非凋亡微粒水平差异无统计学意义。ACS患者划分为聚类A(低水平凋亡微粒)和聚类B(高水平凋亡微粒),聚类B患者STEMI患病率明显高于聚类A(60%vs.32%,P=0.016),而且聚类B的FMD明显下降[(5.2±2.5)vs.(4.1±2.3)%,P=0.02]。两个聚类在冠心病危险因素和全身炎症反应方面均无差别。结论:ACS患者循环凋亡微粒水平明显升高。凋亡微粒为患者临床特征,与ACS患者内皮功能障碍及斑块破裂有关。

Objective:To investigate the effect of circulating apoptotic microparticles on acute coronary syndrome(ACS).Methods:One hundred and twenty-two patients with ACS undertaking coronary an-giography were prospectively enrolled in our hospital from February 2016 to July 2018.Of these patients,49 were ST-elevation myocardial infarction(STEMI),35 were non-STEMI,and 38 were unstable angina.The con-trol groups included 15 patients with stable angina and 16 with normal coronary angiography.Venous blood sam-ples were collected before coronary angiography.Flow cytometry analysis was used to quantify endothelial cell(EMP),red blood cell(RMP)and platelet(PMP)derived microparticles.Apoptotic and non-apoptotic mi-croparticles were assessed using Annexin V staining.Flow-mediated dilatation(FMD)of the brachial artery was assessed by ultrasound to estimate endothelial function.Hierarchical clustering of the patients with ACS were performed based on plasma apoptotic microparticles levels.Results:The levels of apoptotic microparticles were significantly increased in patients with ACS(apoptotic EMP,P<0.0001;apoptotic RMP,P=0.002;apoptotic PMP,P=0.01).There was no difference in the levels of non-apoptotic microparticles among groups.Patients with ACS were divided in cluster A(low level of apoptotic microparticles)and cluster B(high level of apoptotic microparticles).The prevalence of STEMI in cluster B was higher than that in cluster A(60%vs.32%,P=0.016).FMD in cluster B was significantly reduced compared to that in cluster A[(5.2±2.5)vs.(4.1±2.3)%,P=0.02].No differences were found in coronary risk factors and systemic inflammation be-tween the two clusters.Conclusions:The levels of circulating apoptotic cell-derived MP are increased in patients with ACS.Apoptotic microparticles are correlated with impaired endothelial function and plaque rupture in patients with ACS independently of their clinical profile.