急性心肌梗死患者外周血内皮细胞微粒miR-126和线粒体成分及黏附分子表达水平及其临床意义研究

Levels of Endothelial Cell Microparticles miR-126,Mitochondrial Components and Adhesion Molecules in Peripheral Blood of Patients with Acute Myocardial Infarction and Their Clinical Significance

背景急性心肌梗死(AMI)是常见的心血管疾病之一,尽管目前心肌坏死的生物标志物被广泛应用,但AMI的发病率和死亡率仍然居高不下。目的探究内皮细胞微粒(EMPs)内含miR-126、线粒体成分、黏附分子的表达水平及临床意义。方法纳入2021年9月—2022年9月于新疆维吾尔自治区人民医院就诊的AMI患者50例(AMI组)、稳定性冠心病(SCAD)患者50例(SCAD组)、健康者50例(Control组),AMI患者和SCAD患者均在本院住院并接受冠状动脉介入治疗(PCI),健康者均经过本院体检中心的评估。收集三组外周血标本及一般资料,利用透射电镜观察微粒的形态,流式细胞术鉴定EMPs水平,荧光定量PCR检测EMPs中miR-126的表达,ELISA检测EMPs中线粒体活性氧(ROS)及内含黏附分子[血管细胞黏附分子1(VCAM-1)、细胞间黏附分子1(ICAM-1)、E-选择素、P-选择素]的水平。结果通过透射电镜观察到,分离的微粒膜结构完整,直径在100~400 nm。与Control组相比,AMI组血浆EMPs中miR-126表达水平下降(P<0.001),ROS表达水平升高(P<0.001),VCAM-1表达水平升高(P=0.019),ICAM-1表达水平升高(P<0.001),E-选择素表达水平升高(P=0.019),P-选择素表达水平升高(P<0.001)。多因素Logistic回归分析结果显示,miR-126表达水平降低(OR=0.026,95%CI=0.003~0.210,P=0.001)是AMI的保护因素,ROS(OR=1.009,95%CI=1.005~1.013,P<0.001)、P-选择素表达水平升高(OR=1.063,95%CI=1.022~1.105,P=0.002)是AMI的危险因素。受试者工作特征(ROC)曲线显示,miR-126诊断AMI的ROC曲线下面积(AUC)为0.816,ROS诊断AMI的AUC为0.892,P-选择素诊断AMI的AUC为0.728,miR-126、ROS、P-选择素联合诊断AMI的AUC为0.950。结论EMPs中miR-126、ROS、P-选择素以及三者联合指标均对AMI有诊断价值,并且三者联合指标诊断价值最高,这表明其可能为AMI患者的潜在诊断指标。

Background Acute myocardial infarction(AMI)is one of the common cardiovascular diseases,and despite the widespread use of biomarkers for myocardial necrosis,morbidity and mortality of AMI remain high.Objective To investigate the expression levels and clinical significance of miR-126,mitochondrial components and adhesion molecules in endothelial microparticles(EMPs).Methods A total of 50 patients with AMI(AMI group),50 patients with stable coronary artery disease(SCAD)(SCAD group)and 50 healthy subjects(control group)were enrolled in the People's Hospital of Xinjiang Uygur Autonomous Region from September 2021 to September 2022.AMI patients and SCAD patients were hospitalized in our hospital and received percutaneous coronary intervention(PCI),and all healthy subjects were evaluated by the physical examination center of our hospital.Peripheral blood samples and general data of three groups were collected.The morphology of the microparticles(MPs)was observed by transmission electron microscopy(TEM),the level of EMPs was identified by flow cytometry,and the expression of miR-126 in EMPs was detected by fluorescence quantitative PCR.ELISA was used to detect the levels of mitochondrial reactive oxygen species(ROS)and intracellular adhesion molecules[vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),E-selectin,and P-selectin]in EMPs.Results As observed by TEM,the membrane structure of the isolated MPs was intact and its diameter ranged from 100 to 400 nm.Compared with the control group,the expression of miR-126 in plasma EMPs in the AMI group was significantly decreased(P<0.001),the expression of ROS was significantly increased(P<0.001),the expression of VCAM-1 was increased(P=0.019),and the expression of ICAM-1(P<0.001),E-selectin(P=0.019)and P-selectin(P<0.001)were increased.Multivariate Logistic regression analysis showed that the decreased expression of miR-126(OR=0.026,95%CI=0.003-0.210,P=0.001)was a protective factor for AMI,increased expression of ROS(OR=1.009,95%CI=1.005-1.013,P<0.001)and P-selectin(OR=1.063,95%CI=1.022-1.105,P=0.002)were risk factors for AMI.The receiver operator characteristic curve(ROC)showed that the area under the curve of miR-126 for the diagnosis of AMI was 0.816,the area under the curve of ROS for the diagnosis of AMI was 0.892,the area under the curve of P-selectin for the diagnosis of AMI was 0.728,and the area under the curve of miR-126,ROS and P-selectin combined diagnosis was 0.950.Conclusion In EMPs,miR-126,ROS,P-selectin and their combined indicators all have diagnostic value for AMI,and the combined indicators of the three have the highest diagnostic value,indicating that they may be potential diagnostic indicators for AMI patients.