Department of Emergency, Yidu Central Hospital of Weifang, No. 4138, South Linglongshan Road, Weifang, 262500, Shandong, China.
Eur J Med Res. 2020 Mar 17;25(1):2. doi: 10.1186/s40001-020-00403-8.
Acute coronary syndrome (ACS) is a serious type of cardiovascular diseases. This study aimed to investigate the expression patterns and clinical value of microRNA-145 (miR-145) in ACS patients, and further uncover the function of miR-145 in ACS rats.
Quantitative real-time PCR was used to estimate the expression of miR-145. Diagnostic value of miR-145 was evaluated, and its correlation with endothelial injury marker (vWF and H-FABP) and pro-inflammatory cytokines (IL-6 and TNF-α) was analyzed. Coronary artery ligation was adopted to construct the ACS rat model, and the effects of miR-145 on endothelial injury, inflammation and vascular endothelial cells (VECs) biological function were examined.
Downregulated expression of miR-145 was found in the ACS serum samples compared with the healthy controls. The expression of miR-145 was proved to be a diagnostic biomarker and negatively correlated with vWF, H-FABP, IL-6 and TNF-α. The similar serum expression trends of miR-145 in ACS patients were also observed in the ACS rats, and the overexpression of miR-145 could decrease the elevated vWF, H-FABP, IL-6 and TNF-α in the animal model. Moreover, the upregulation of miR-145 in VECs led to promoted proliferation and migration. The bioinformatics prediction data and luciferase report results indicated that FOXO1 was a direct target of miR-145.
In conclusion, it was hypothesized that serum decreased expression of miR-145 may serve as a potential diagnostic biomarker in ACS patients. Overexpression of miR-145 may improve the endothelial injury and abnormal inflammation through targeting FOXO1, indicating that miR-145 serves as a candidate therapeutic target of ACS.
急性冠状动脉综合征（ACS）是一种严重的心血管疾病。本研究旨在探讨 microRNA-145（miR-145）在 ACS 患者中的表达模式及其临床价值，并进一步揭示 miR-145 在 ACS 大鼠中的作用。
采用实时定量 PCR 估计 miR-145 的表达。评估 miR-145 的诊断价值，并分析其与内皮损伤标志物（vWF 和 H-FABP）和促炎细胞因子（IL-6 和 TNF-α）的相关性。采用冠状动脉结扎构建 ACS 大鼠模型，观察 miR-145 对内皮损伤、炎症和血管内皮细胞（VEC）生物学功能的影响。
与健康对照组相比，ACS 血清样本中 miR-145 的表达下调。miR-145 的表达被证明是一种诊断生物标志物，与 vWF、H-FABP、IL-6 和 TNF-α呈负相关。在 ACS 大鼠中也观察到 ACS 患者血清中 miR-145 的相似表达趋势，miR-145 的过表达可降低动物模型中升高的 vWF、H-FABP、IL-6 和 TNF-α。此外，miR-145 在 VEC 中的上调可促进增殖和迁移。生物信息学预测数据和荧光素酶报告结果表明，FOXO1 是 miR-145 的直接靶标。
总之，研究假设血清中 miR-145 的表达降低可能是 ACS 患者的潜在诊断生物标志物。miR-145 的过表达可能通过靶向 FOXO1 改善内皮损伤和异常炎症，表明 miR-145 是 ACS 的候选治疗靶点。
