Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
J Neurosci Res. 2020 Nov;98(11):2290-2301. doi: 10.1002/jnr.24696. Epub 2020 Jul 29.
Endothelial microvesicles (EMVs) could reflect the status of endothelial cells (ECs) which are involved in the pathogenesis of ischemic stroke (IS). MiR-155 could regulate EC functions. However, their roles in IS remain unclear. This study aimed to investigate the levels of plasma EMVs and EMVs carrying miRNA-155 (EMVs-miR-155) in IS patients to explore their potential roles as biomarkers. Ninety-three IS patients and 70 controls were recruited in this study. The levels of circulating EMVs and EMVs-miR-155 were detected by fluorescence nanoparticle tracking analysis and quantitative real-time PCR, respectively. The correlations between level of EMVs/EMVs-miR-155 and the onset time, severity, infarct volume, and subtypes of IS were analyzed. The severity and infarct volume were assessed by NIHSS and magnetic resonance imaging, respectively. Multivariate logistic regression analysis was used to investigate the risk factors of IS. The ROC curve and area under ROC curve (AUC) of EMVs and EMVs-miR-155 were determined. The levels of plasma EMVs and EMVs-miR-155 were increased significantly in acute and subacute stages of IS and remained unchanged in chronic stage, and were positively related to the infarct volume and NIHSS scores and were associated with large artery atherosclerosis and cardioembolism subtypes defined by Trial of Org 10 172 in acute stroke treatment (TOAST) classification. Multivariate logistic regression analysis demonstrated that plasma EMVs and EMVs-miR-155 were significant and independent risk factors of IS and their AUC were 0.778 and 0.851, respectively, and increased to 0.892 after combination. Our study suggests that plasma EMVs and EMVs-miR-155 are promising biomarkers for IS. The diagnostic value of EMVs-miR-155 is higher and their combination is the best.
内皮细胞来源的微小囊泡 (endothelial microvesicles, EMVs) 可以反映内皮细胞 (endothelial cells, ECs) 的状态，而 ECs 参与了缺血性脑卒中 (ischemic stroke, IS) 的发病机制。miR-155 可以调节 ECs 的功能。然而，其在 IS 中的作用尚不清楚。本研究旨在探讨 IS 患者血浆 EMVs 及其携带的 miRNA-155（EMVs-miR-155）的水平，以探索其作为生物标志物的潜在作用。本研究纳入了 93 例 IS 患者和 70 例对照者。通过荧光纳米颗粒跟踪分析和实时定量 PCR 分别检测循环 EMVs 和 EMVs-miR-155 的水平。分析 EMVs/EMVs-miR-155 水平与 IS 发病时间、严重程度、梗死体积和亚型之间的相关性。采用 NIHSS 评分和磁共振成像评估严重程度和梗死体积。采用多变量 logistic 回归分析探讨 IS 的危险因素。通过绘制受试者工作特征曲线 (receiver operating characteristic curve, ROC) 及其曲线下面积 (area under ROC curve, AUC)，评估 EMVs 和 EMVs-miR-155 的诊断效能。IS 急性和亚急性期患者的血浆 EMVs 和 EMVs-miR-155 水平显著升高，慢性期无变化，且与梗死体积和 NIHSS 评分呈正相关，与大动脉粥样硬化和 Trial of Org 10172 in Acute Stroke Treatment (TOAST) 分类定义的心源性栓塞亚型相关。多变量 logistic 回归分析表明，血浆 EMVs 和 EMVs-miR-155 是 IS 的显著且独立的危险因素，其 AUC 分别为 0.778 和 0.851，联合后增加至 0.892。本研究表明，血浆 EMVs 和 EMVs-miR-155 是 IS 有潜力的生物标志物，其中 EMVs-miR-155 的诊断价值更高，两者联合应用效果最佳。
