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<p>Carotid artery stenosis (CAS) is a major cerebrovascular disease and a leading cause of cerebral ischemic events (CIEs). However, the early identification of CAS patients at high risk of progressing to CIEs remains a significant clinical challenge. MicroRNAs, particularly miR-221-3p, have gained research focus for their roles in various pathologies. To evaluate the diagnostic value of miR-221-3p in CAS and elucidate its functional mechanisms. This study enrolled 90 CAS patients and 75 hypertensive controls. Serum miR-221-3p levels were measured by qRT-PCR. Its diagnostic and predictive value was assessed using ROC, logistic regression, and Cox analyses. Cellular effects were evaluated using an ox-LDL-induced human aortic endothelial cells (HAECs) injury model. The miR-221-3p and MYBL1 interaction was verified by luciferase reporter assay, followed by rescue experiments. miR-221-3p levels exhibited a significant upregulation in serum of CAS patients (<i>P</i> &lt; 0.001) and served as an independent risk factor for hypertension patients progressing to CAS (OR = 7.489). It exhibited strong diagnostic value for CAS (AUC = 0.837). Additionally, the positive association between miR-221-3p upregulation and CAS severity (<i>P</i> &lt; 0.001). miR-221-3p was a risk factor for CIEs among CAS patients (HR = 6.421). Functional experiments revealed that inhibiting miR-221-3p reversed ox-LDL-induced damage in HAECs. The direct targeting of MYBL1 by miR-221-3p was verified via the dual-luciferase reporter system. The protective effect of down-regulating miR-221-3p on ox-LDL-induced HAECs injury was significantly reversed by si-MYBL1. Elevated expression of miR-221-3p was observed in CAS and could function as a potential biomarker. miR-221-3p exacerbates ox-LDL-induced injury in HAECs by targeting MYBL1.</p> Graphical Abstract <p></p>

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miR-221-3p mediates endothelial injury and predicts cerebral ischemic in carotid artery stenosis

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Yanbin Huang,
  • Lifen Wang,
  • Lihong Ren,
  • Danian Liu,
  • Xiaolin Wu

摘要

Carotid artery stenosis (CAS) is a major cerebrovascular disease and a leading cause of cerebral ischemic events (CIEs). However, the early identification of CAS patients at high risk of progressing to CIEs remains a significant clinical challenge. MicroRNAs, particularly miR-221-3p, have gained research focus for their roles in various pathologies. To evaluate the diagnostic value of miR-221-3p in CAS and elucidate its functional mechanisms. This study enrolled 90 CAS patients and 75 hypertensive controls. Serum miR-221-3p levels were measured by qRT-PCR. Its diagnostic and predictive value was assessed using ROC, logistic regression, and Cox analyses. Cellular effects were evaluated using an ox-LDL-induced human aortic endothelial cells (HAECs) injury model. The miR-221-3p and MYBL1 interaction was verified by luciferase reporter assay, followed by rescue experiments. miR-221-3p levels exhibited a significant upregulation in serum of CAS patients (P < 0.001) and served as an independent risk factor for hypertension patients progressing to CAS (OR = 7.489). It exhibited strong diagnostic value for CAS (AUC = 0.837). Additionally, the positive association between miR-221-3p upregulation and CAS severity (P < 0.001). miR-221-3p was a risk factor for CIEs among CAS patients (HR = 6.421). Functional experiments revealed that inhibiting miR-221-3p reversed ox-LDL-induced damage in HAECs. The direct targeting of MYBL1 by miR-221-3p was verified via the dual-luciferase reporter system. The protective effect of down-regulating miR-221-3p on ox-LDL-induced HAECs injury was significantly reversed by si-MYBL1. Elevated expression of miR-221-3p was observed in CAS and could function as a potential biomarker. miR-221-3p exacerbates ox-LDL-induced injury in HAECs by targeting MYBL1.

Graphical Abstract