Circulating pro-angiogenic and anti-angiogenic microRNA expressions in patients with acute ischemic stroke and their association with disease severity

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Abstract
The main objectives of this study are to evaluate 28 selected pro-angiogenic and anti-angiogenic microRNA (miRNA) expressions in plasma of acute ischemic stroke (AIS) patients and controls and to assess the correlations of these miRNAs with risk and severity of AIS. In the exploring stage, 10 AIS patients and 10 controls with vascular risk factors were enrolled. And in the validating stage, 106 AIS patients and 110 controls with the same eligibility were recruited. Blood samples were collected from participants within 24 h post the onset of symptoms, and plasma levels of miRNAs were evaluated by the qPCR method. In the exploring stage, 11 differentially expressed miRNAs (DEM) were identified and included into the validating stage. In the validating stage, the expression of miR-126, miR-130a, and miR-378 in plasma declined in the AIS patients; however, miR-222, miR-218, and miR-185 plasma levels were elevated. Univariate and multivariate logistic regression analysis disclosed that miR-126, miR-130a, miR-222, miR-218, and miR-185 were independent predicting factors for AIS. When these five DEMs were combined together, they presented a good diagnostic value with an area under curve (AUC) value of 0.767 (95% CI 0.705–0.829), sensitivity of 87.7%, and specificity of 54.5% at best cutoff point. Additionally, miR-126, miR-378, miR-101, miR-222, miR-218, and miR-206 were associated with National Institutes of Health Stroke Scale (NIHSS) score. Circulating miR-126, miR-130a, miR-222, miR-218, and miR-185 could be served as promising and independent biomarkers for risk of AIS, and miR-126, miR-378, miR-222, miR-101, miR-218, and miR-206 could be used for disease severity management of AIS.

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