Zhu Bin, Liu Wei, Xu Qiang, Liu Hong-Liang
Department of Neurosurgery, Renhe Hospital, Baoshan District, Shanghai, People's Republic of China.
J Inflamm Res. 2022 May 30;15:3207-3217. doi: 10.2147/JIR.S362774. eCollection 2022.
Carotid artery stenosis (CAS) is a leading cause of cerebral infarction, its early diagnosis and intervention are necessary. In light of the important role of microRNAs (miRNAs) in cerebrovascular disease, this study aimed to investigate the expression pattern and clinical significance of serum miR-455-5p in the onset and development of CAS, as well as its underlying mechanism.
Seventy patients with asymptomatic CAS were recruited, and the development of cerebral ischemia events (CIEs) was recorded during the five-years follow-up. qRT-PCR was performed for the serum miR-455-5p detection. ROC curve was applied for the diagnostic ability evaluation. By constructing multivariable logistic or cox regression model, odds ratio (OR) or hazard ratio (HR) were calculated to assess the impact of each risk factor on independent variables. Human aortic endothelial cells (HAECs) were treated with ox-LDL to induce endothelial cell damage. The role of miR-455-5p in the cell viability, apoptosis, oxidative stress and inflammatory response was detected.
Serum miR-455-5p showed low expression in cases with CAS, and had an independent influence on the degree of CAS. The diagnostic ability of serum miR-455-5p to diagnose CAS was determined via ROC curve, with the AUC of 0.927. During follow-up, patients with low miR-455-5p expression showed high incidence of CIEs. In multivariable cox regression model, degree of CAS and miR-455-5p were significant risk factors for the development of CIEs in the CAS patients. In vitro, miR-455-5p was at a low expression in HAECs cell models and can prevent cells from ox-LDL induced cell apoptosis, oxidative stress and inflammatory response. SOCS3 was a target gene of miR-455-5p and upregulated in ox-LDL treated cells.
Down-regulated expression of serum miR-455-5p is hopeful to be used as a biomarker for the early diagnosis of CAS. MiR-455-5p is an independent risk factor for the degree of CAS, and has a certain predictive value for the development of CIEs. That might be associated with the protective role of miR-455-5p against ox-LDL-induced endothelial cell injury via targeting SOCS3.
颈动脉狭窄（CAS）是脑梗死的主要原因，其早期诊断和干预很有必要。鉴于微小RNA（miRNA）在脑血管疾病中的重要作用，本研究旨在探讨血清miR-455-5p在CAS发生发展中的表达模式、临床意义及其潜在机制。
招募70例无症状CAS患者，记录五年随访期间脑缺血事件（CIE）的发生情况。采用qRT-PCR检测血清miR-455-5p。应用ROC曲线评估诊断能力。通过构建多变量逻辑回归或Cox回归模型，计算比值比（OR）或风险比（HR），以评估各危险因素对自变量的影响。用人主动脉内皮细胞（HAECs）经氧化型低密度脂蛋白（ox-LDL）处理诱导内皮细胞损伤。检测miR-455-5p在细胞活力、凋亡、氧化应激和炎症反应中的作用。
血清miR-455-5p在CAS患者中呈低表达，且对CAS程度有独立影响。通过ROC曲线确定血清miR-455-5p诊断CAS的能力，AUC为0.927。随访期间，miR-455-5p低表达患者CIE发生率高。在多变量Cox回归模型中，CAS程度和miR-455-5p是CAS患者发生CIE的显著危险因素。体外实验中，miR-455-5p在HAECs细胞模型中低表达，可防止细胞因ox-LDL诱导的细胞凋亡、氧化应激和炎症反应。信号转导和转录激活因子3（SOCS3）是miR-455-5p的靶基因，在ox-LDL处理的细胞中上调。
血清miR-455-5p表达下调有望作为CAS早期诊断的生物标志物。miR-455-5p是CAS程度的独立危险因素，对CIE的发生有一定预测价值。这可能与miR-455-5p通过靶向SOCS3对ox-LDL诱导的内皮细胞损伤的保护作用有关。
