MicroRNA-486-5p functions as a diagnostic marker for carotid artery stenosis and prevents endothelial dysfunction through inhibiting inflammation and oxidative stress

Abstract

Carotid artery stenosis (CAS) can cause ischemic stroke, and clinical intervention for CAS is critical clinically. The purpose of this study was to explore the expression changes of microRNA-486-5p in the serum of patients with CAS and its possible mechanism. Ninety-one cases with asymptomatic CAS were recruited, and serum levels of miR-486-5p were measured using RT-qPCR. The diagnostic ability was evaluated by drawing the receiver operating characteristic (ROC) curve. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (oxLDL) to establish cell model, and cell proliferation and apoptosis were tested. The markers of cell inflammation and oxidative stress were detected via ELISA. The target gene was analyzed using bioinformatics analysis combined with luciferase reporting assay. CAS cases exhibited significantly low serum miR-486-5p levels in comparison with the control group and can identify asymptomatic CAS. Serum miR-486-5p manifested a negative correlation with the degree of carotid stenosis. Underexpression of miR-486-5p was also detected in ox-LDL treated HAECs. OxLDL treatment contributes to inflammatory response and oxidative stress of HAECs; however, these adverse impacts caused by ox-LDL were reversed by miR-486-5p upregulation. NFAT5 was confirmed to be the target gene of miR-486-5p in HAECs. MiR-486-5p serves as a promising biomarker for the early identification of CAS. Overexpression of miR-486-5p can prevent endothelial dysfunction, and the mechanism might be related to anti-inflammation and anti-oxidation via targeting NFAT5.

Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions

“…In addition, previous reports characterized miR-155 and miR-122 as suppressors of cell migration and oxidative stress, including vascular SMC ( Tong et al, 2023 ), whereas knockdown of miR-155-5p results in increased proliferation and migration of human brain micro-vessel ECs ( Liu et al, 2015 ). Another significantly upregulated lncRNA, ENSMUST00000131663, had potential binding sites for miR-486-5p, which is known to function as a diagnostic marker for carotid artery stenosis and preventing endothelial dysfunction by inhibiting inflammation and oxidative stress ( Zhu et al, 2022 ).…”

Joint High Level of Oxidized Low‐Density Lipoprotein and High‐Sensitivity C‐Reactive Protein are Associated With Recurrent Stroke and Poor Functional Outcome in Minor Stroke or Transient Ischemic Attack

“… 16 A recent animal study found that oxLDL treatment contributes to the inflammatory response and oxidative stress in human aortic endothelial cells, linking oxLDL and C‐reactive protein to atherosclerosis, endothelial dysfunction, oxidative stress, and inflammatory response from a molecular perspective. 28 However, the evidence on the association of combined oxLDL and hs‐CRP with poor prognosis after stroke is limited. In the current study, we used the upper quartile of oxLDL and hs‐CRP to differentiate between high and low risk, and found the association of oxLDL and hs‐CRP and adverse vascular outcomes appears only at both high levels, when both low levels treated as the reference group, which is in accord with other studies on the association of oxLDL and hs‐CRP with coronary events.…”

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis

“…Furthermore, the downregulation of miR-206, miR-9-5p, and miR-637 in the patients had predictive value for the incidence of cerebrovascular events within 5 years [ 181 , 182 , 183 ]. Interestingly, an in vitro proliferation assay indicated that overexpression of miR-503-5p significantly inhibited the proliferation of VSMCs, thus improving atherosclerosis [ 184 ] and that miR-486-5p prevented endothelial dysfunction in association with an anti-inflammatory and antioxidative effect by targeting the nuclear factor of activated T cells 5 (NFAT5) [ 185 ].…”