MicroRNA-363-3p serves as a diagnostic biomarker of acute myocardial infarction and regulates vascular endothelial injury by targeting KLF2
MicroRNA-363-3p serves as a diagnostic biomarker of acute myocardial infarction and regulates vascular endothelial injury by targeting KLF2
复制标题
DOI：
10.21037/cdt-19-700
复制
发表时间：
2020-06-01
影响因子：
2.4
通讯作者：
Zhang, Hua
中科院分区：
文献类型：
--
作者：
Gao, Chao;Qian, Hengbo;Zhang, Hua
背景：急性心肌梗死（AMI）是一种严重的心血管疾病。本研究旨在探讨microRNA-363- 3 p（miR-363- 3 p）在AMI患者中的诊断价值，并探讨miR-363 - 3 p在AMI大鼠模型血管内皮损伤中的作用。绘制受试者工作特征（ROC）曲线以评估miR-363- 3 p在AMI患者中的诊断价值。使用酶联免疫吸附测定法估计内皮损伤的生物标志物，并评估miR-363- 3 p与这些标志物的相关性。采用冠状动脉结扎法建立大鼠急性心肌梗死模型，观察miR-363 - 3 p对血管内皮细胞损伤和增殖的影响。血清中miR-363- 3 p的升高可作为AMI的候选诊断生物标志物。相关性分析显示，AMI患者血清miR-363- 3 p表达与内皮损伤标志物浓度呈正相关。此外，miR-363 - 3 p的敲低可抑制AMI大鼠内皮损伤生物标志物的增加，并明显促进人脐静脉内皮细胞的增殖。预测结果显示Kruppel样因子2（KLF 2）是miR-363- 3 p的靶点，并通过荧光素酶报告基因分析证实了它们之间的相互作用。总的来说，miR-363- 3 p的过表达作为AMI患者的诊断生物标志物，miR-363- 3 p的下调通过靶向KLF 2改善AMI相关的内皮损伤，提示miR-363- 3 p具有开发AMI治疗的潜力。
Background: Acute myocardial infarction (AMI) is a serious cardiovascular disease. This study aimed to investigate the diagnostic value of microRNA-363-3p (miR-363-3p) in AMI patients and explore the effects of miR-363-3p on vascular endothelial injury in an AMI rat model.Methods: The Expression of miR-363-3p was measured by quantitative real-time PCR. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of miR-363-3p in AMI patients. The biomarkers of endothelial injury were estimated using enzyme-linked immunosorbent assays, and the correlation of miR-363-3p with these markers was assessed. AMI rat model was constructed using coronary artery ligation, and the effects of miR-363-3p on endothelial injury and endothelial cell proliferation were analyzed.Results: Serum expression of miR-363-3p was upregulated in the AMI patients compared with healthy controls. The increased serum miR-363-3p serves a candidate diagnostic biomarker of AMI. The correlation analysis indicated that serum miR-363-3p expression was positively correlated with the concentration of endothelial injury biomarkers in AMI patients. Furthermore, the increased endothelial injury biomarkers in AMI rats were all inhibited by the knockdown of miR-363-3p, and the cell proliferation of human umbilical vein endothelial cells was obviously enhanced by the reduction of miR-363-3p. The prediction results shown that Kruppel-like factor 2 (KLF2) is a target of miR-363-3p, and their interaction was proved using a luciferase reporter assay.Conclusions: Collectively, overexpression of miR-363-3p acts as a diagnostic biomarker for patients with AMI, and the downregulation of miR-363-3p improves AMI-associated endothelial injury by targeting KLF2, which indicated that miR-363-3p has a potential to develop the treatment of AMI.