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MicroRNA-503-5p improves carotid artery stenosis by inhibiting the proliferation of vascular smooth muscle cells.

ABSTRACT: Carotid artery stenosis (CAS) is a common arteriosclerotic vascular disease affected by vascular smooth muscle cells (VSMCs). The aim of the present study was to investigate the expression and diagnostic value of microRNA (miR)-503-5p in asymptomatic patients with CAS and to further explore the effect of miR-503-5p on VSMC proliferation. The levels of miR-503-5p in the serum of 62 asymptomatic patients with CAS and 60 healthy controls were detected by reverse transcription-quantitative PCR. The association between miR-503-5p and the clinical characteristics of the patients was analyzed using the ?2 test. A receiver operating characteristic curve was drawn to evaluate the diagnostic value of miR-503-5p to distinguish asymptomatic patients with CAS from healthy controls. Finally, miR-503-5p inhibitors and mimics were transfected into VSMCs in vitro to detect the effect of miR-503-5p on the proliferation ability through Cell Counting Kit-8 assays. The serum levels of miR-503-5p in asymptomatic patients with CAS were significantly reduced as compared with those in healthy individuals. The expression levels of miR-503-5p were significantly associated with diabetes and arterial stenosis. Furthermore, the area under the ROC curve was 0.817, the specificity was 79.03% and the sensitivity was 83.30%, which proved that miR-503-5p had a high diagnostic accuracy in patients with CAS. Finally, the in vitro proliferation assay indicated that overexpression of miR-503-5p significantly inhibited the proliferation of VSMCs. In conclusion, miR-503-5p is a potential diagnostic biomarker for asymptomatic CAS and overexpression of miR-503-5p may inhibit the proliferation of VSMCs and improve CAS.

SUBMITTER: Yan Z

PROVIDER: S-EPMC7500050 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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MicroRNA-503-5p improves carotid artery stenosis by inhibiting the proliferation of vascular smooth muscle cells.

Yan Zhiyuan Z Wang Hong H Liang Junjun J Li Yuan Y Li Xiaodong X

Experimental and therapeutic medicine 20200911 5

Carotid artery stenosis (CAS) is a common arteriosclerotic vascular disease affected by vascular smooth muscle cells (VSMCs). The aim of the present study was to investigate the expression and diagnostic value of microRNA (miR)-503-5p in asymptomatic patients with CAS and to further explore the effect of miR-503-5p on VSMC proliferation. The levels of miR-503-5p in the serum of 62 asymptomatic patients with CAS and 60 healthy controls were detected by reverse transcription-quantitative PCR. The ...[more]

PMID: 32968442

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Project description:BackgroundAtherosclerosis is the main cause of carotid artery stenosis (CAS) which mostly occurs in the elderly. In this paper, the expression level of miR-375-3p in asymptomatic CAS patients and its diagnostic value for asymptomatic CAS were investigated, and the effects of miR-375-3p on the cell proliferation and migration of vascular smooth muscle cells (VSMCs) was further explored.Methods98 healthy subjects and 101 asymptomatic CAS patients were participated in this study. qRT-PCR was used to measure the expression level of serum miR-375-3p, and the ROC curve was established to evaluate the predictive value of miR-375-3p for asymptomatic CAS. After transfection with miR-375-3p mimic or inhibitor in vitro, cell proliferation and migration were detected by CCK-8 assay, colony formation assay, and Transwell assay, respectively. The levels of TNF-α, IL-1β, IL-6 were detected by ELISA. Western blot was used to detect the protein expression of XIAP. Finally, luciferase reporter gene assay was applied to assess the interaction of miR-375-3p with target genes.ResultsThe expression level of serum miR-375-3p in asymptomatic CAS patients was significantly higher than that in healthy controls, and the AUC value of ROC curve was 0.888. The sensitivity and specificity were 80.2 and 86.7%, respectively, indicating that miR-375-3p had high diagnostic value for asymptomatic CAS. In vitro cell experiments showed that up-regulation of miR-375-3p significantly promoted the proliferation and migration of VSMCs, and also promoted the generation of inflammatory factors and phenotypic transformation of VSMCs. Luciferase reporter gene assay confirmed that XIAP was a target gene of miR-375-3p and was negatively regulated by miR-375-3p.ConclusionsIn this study, miR-375-3p may have a clinical diagnostic value for asymptomatic CAS patients which need further validation. Increased miR-375-3p levels in CAS may be associated with increased proliferation and migration of VSMCs via downregulation of the apoptosis inducing gene XIAP.

Project description:Background: Risk stratification of asymptomatic carotid artery stenosis (ACAS) is still an issue for carotid revascularization. We sought to identify factors associated with symptomatic carotid artery stenosis (SCAS) using multimodal imaging techniques. Methods: We retrospectively collected data on patients who underwent carotid artery revascularization. Results from duplex sonography, computerized tomography angiography, brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), perfusion-weighted imaging, and demographic profiles were compared between ACAS and SCAS patients. Differences in baseline characteristics between the two groups were balanced by the propensity matching score method. Multivariable regression analysis was performed to identify factors associated with symptomaticity of carotid artery stenosis. We compared the strength of associations between significant imaging factors and symptomatic carotid stenosis using C statistics. Results: A total of 259 patients (asymptomatic 57.1%, symptomatic 42.9%) with carotid stenosis were included. After 1:1 propensity score matching, the multivariable regression analysis revealed that the absence of plaque calcification [Odds ratio 0.41, 95% confidence interval (CI) 0.182-0.870, p = 0.023], deep white matter hyperintensity (DWMH; Odds ratio 3.46, 95% CI 1.842-6.682, p < 0.001), susceptibility vessel sign seen on gradient-echo MRI (Odds ratio 2.35, 95% CI 1.113-5.107, p = 0.027), and increased cerebral blood volume (CBV) seen on perfusion-weighted MRI (CBV; Odds ratio 2.17, 95% CI 1.075-4.454, p = 0.032) were associated with SCAS. The combination of these variables had a fair accuracy to classify SCAS (Area under the curve 0.733, 95% CI 0.662-0.803). Conclusions: We identified several multimodal imaging markers independently associated with SCAS. These markers may provide information to identify ACAS patients with high risk of ischemic stroke. Future studies are needed to predict SCAS using our findings in other independent cohorts.

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MicroRNA-503-5p improves carotid artery stenosis by inhibiting the proliferation of vascular smooth muscle cells.

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MicroRNA-503-5p improves carotid artery stenosis by inhibiting the proliferation of vascular smooth muscle cells.

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