Clinical Values and Underlying Mechanism Analysis of Serum miR-455-5p in Carotid Artery Stenosis

Abstract

Purpose 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. Patients and Methods 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. Results 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. Conclusion 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.

LncRNA THRIL Functions as a Marker for Carotid Artery Stenosis and Affects the Biological Function of Human Aortic Endothelial Cell

“…The cells were cultured in an incubator at 37°C and 5% CO 2 and the medium was changed every 2–3 days. The cells in the ox-LDL group were treated with 100 mg/L ox-LDL, 13 the cells in the ox-LDL + small interference negative control (si-NC) group were treated with ox-LDL for 24 h after transfection with si-NC, and the cells in the ox-LDL + si-THRIL group were treated with ox-LDL after transfection with THRIL sequences. When HAECs grew to 80% fusion, they were induced with ox-LDL for 24 h. HAECs were inoculated into a 6-well plate with 5×10 4 cells per well, and Lipofectamine TM 3000 was used to transfect obtained sequences according to the instructions.…”

microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician’s Perspective

“…Some miRNAs were investigated in the context of carotid plaques, including miR-520, miR-455, and miR-105. Some are common for many arterial territories, including miR-21, miR-27, miR-100, and miR-122 ( Table 1 ) [ 45 , 55 , 56 , 57 , 58 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ].…”

“…In a study by Zhu et al, low serum levels of miR-455 were highly diagnostic for a high-grade asymptomatic ICAS, with the AUC value of 0.992, a sensitivity of 82.9%, and a specificity of 90.8% [ 61 ]. The multivariate regression analysis demonstrated that levels of LDL-cholesterol (OR = 4.380, 95% CI = 1.101–17.419, p = 0.036) and miR-455-5p (OR = 0.154, 95% CI = 0.039–0.606, p = 0.007) were independently associated with the severity of ICAS.…”

“…The multivariate regression analysis demonstrated that levels of LDL-cholesterol (OR = 4.380, 95% CI = 1.101–17.419, p = 0.036) and miR-455-5p (OR = 0.154, 95% CI = 0.039–0.606, p = 0.007) were independently associated with the severity of ICAS. Moreover, miR-455 (HR = 0.128, 95% CI = 0.029–0.573, p = 0.007), likewise the degree of ICAS, occurred important risk factors for ICAS-related IS [ 61 ]. The Kaplan–Meier survival curves showed that low miR-455-5p expression was related to the incidence of IS during follow-up (log Rank P = 0.002).…”