Aberrant expression of miR‑483‑5p in patients with asymptomatic carotid artery stenosis and its predictive value for cerebrovascular event occurrence

Abstract

MicroRNAs (miRNAs/miRs) may be used as novel promising diagnostic and prognostic biomarkers for various diseases, including asymptomatic carotid artery stenosis (ACAS). The present study aimed to investigate the abnormal expression of microRNA-483-5p (miR-483-5p) in patients with ACAS and to evaluate its diagnostic value for ACAS screening and its predictive value for cerebrovascular events. A total of 128 patients with ACAS and 76 healthy controls were included in the present study. The expression of miR-483-5p in serum was measured by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-483-5p in patients with ACAS. Kaplan-Meier curves were drawn and Cox regression analysis was used to determine the predictive value of miR-483-5p for cerebrovascular events in patients with ACAS. Serum miR-483-5p levels were significantly increased in patients with ACAS as compared with those in healthy controls. The expression of miR-483-5p was significantly associated with diabetes (P=0.011), dyslipidemia (P=0.047) and the degree of carotid stenosis (P=0.006) in patients with ACAS. In addition, the area under the ROC curve was 0.910, with a sensitivity of 80.5% and a specificity of 89.5% at the cutoff value of 0.705, indicating that serum miR-483-5p expression has a certain diagnostic value in patients with ACAS. Furthermore, the patients with high miR-483-5p expression had a higher proportion of cerebrovascular events than patients with low miR-483-5p levels (log-rank P=0.011) and miR-483-5p was an independent prognostic marker for predicting the occurrence of cerebrovascular events in patients with ACAS. The results indicated that miR-483-5p expression is significantly increased in patients with ACAS and that abnormal miR-483-5p expression may be a candidate biomarker for ACAS diagnosis and the prediction of cerebrovascular event occurrence.

Interplay between microRNAs, Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Lipid Parameters in Patients with Very High Lipoprotein(a) Treated with PCSK9 Inhibitors

“…Increased serum miR-483-5p expression was also reported in patients with asymptomatic carotid artery stenosis compared with controls. At the same time, serum miR-483-5p expression was an independent predictive factor for the occurrence of an acute cerebrovascular event in patients with asymptomatic carotid artery stenosis [ 45 ].…”

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

“…In line with this, Li et al analyzed expression levels of miR-483-5p in patients with asymptomatic ICAS and evaluated its diagnostic and predictive value for IS [ 127 ]. The results revealed that patients with high miR-483-5p levels had higher a risk of IS (log-rank p = 0.011), as compared to patients with lower miR-483-5p expression levels (HR 2.670; 95% CI 1.099–6.484; p = 0.030) [ 127 ]. Similarly, miR-342-5p was proposed as an IS risk predictor at a 5 year follow-up by Zhou et al [ 128 ].…”

Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis

“…miR-106-5p was also significantly upregulated in the serum of ACAS patients, which could regulate cholesterol efflux targeting ABCA1 [80,86]. miR-483-5p has also been found to be increased in the serum of ACAS patients versus healthy controls, and its underlying regulatory pathway could be the regulation of high cholesterol by targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), affecting the development of ACAS [87]. Moreover, upregulation of miR-92a could also be a non-invasive serum biomarker for ACAS, which might be involved in the inflammatory response by enhancing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [71,88] in the dysregulation of endothelial progenitor cells by targeting growth differentiation factor 11 (GDF11) via the SMAD2/3/FAK/AKT/eNOS pathway [71,89] and in the progression of atherosclerosis through the targeting of ABCA1 [71,90], as mentioned above for miR-106-5p.…”

“…In addition, the Kaplan-Meier method has been used to assess the predictive value of the occurrence of cerebrovascular ischaemic events (CIE) in some of the miRNAs discussed above. Multivariate Cox regression analysis suggests that altered serum levels of miR-186-5p [74], miR-106-5p [80], miR-483-5p [87], miR-92a [71], miR-342-5p [69], and miR-9-5p [75] could predict the risk of future cerebrovascular events. This would mean that they might also be valuable predictors of CIE and instability.…”