Jin Yan, Yang Cheng-Jian, Xu Xin, Cao Jia-Ning, Feng Qiu-Ting, Yang Jun
Department of Cardiology, Wuxi No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, China.
Mol Cell Biochem. 2015 Apr;402(1-2):111-22. doi: 10.1007/s11010-014-2319-5. Epub 2015 Jan 10.
Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-214 and the expression of vascular endothelial growth factor (VEGF) in the pathogenesis of coronary heart disease patients to further explore the mechanism involved in the vasculogenesis. Three different cohorts, including 13 acute myocardial infarction patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-214 in patients with myocardial ischemia and also the relationship between plasma miR-214 and severity of coronary stenosis. Plasma miR-214 levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I concentrations were measured by ELISA assays. We further detected the correlation of miR-214 and VEGF by molecular and animal assays. MiR-214 was enriched in not only diseased endothelial progenitor cells (EPCs) but also the plasma of coronary artery disease (CAD) patients. Besides, we found out miR-214 was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-214 to the 39-UTR of VEGF mRNA. Knockdown of miR-214 not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but also further promoted blood flow recovery in ischemic limbs of mice. Circulating miR-214 may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-214 level may be used to predict the presence and severity of coronary lesions in CAD patients.
患者体液中的循环微小RNA（miRNA）最近被认为具有成为新型疾病生物标志物和药物靶点的潜力。我们旨在研究冠心病患者发病机制中循环miR-214水平与血管内皮生长因子（VEGF）表达之间的相关性，以进一步探索血管生成所涉及的机制。纳入了三个不同的队列，包括13例急性心肌梗死患者、176例心绞痛患者和127例对照受试者，以研究心肌缺血患者循环miR-214的表达水平以及血浆miR-214与冠状动脉狭窄严重程度之间的关系。通过实时定量PCR检测参与者的血浆miR-214水平。同时，通过ELISA测定法测量血浆心肌肌钙蛋白I浓度。我们通过分子和动物实验进一步检测了miR-214与VEGF的相关性。miR-214不仅在患病的内皮祖细胞（EPC）中富集，而且在冠状动脉疾病（CAD）患者的血浆中也有富集。此外，我们发现miR-214能够抑制VEGF表达和EPC活性。报告基因实验证实了miR-214与VEGF mRNA的3′-UTR直接结合并具有抑制作用。敲低miR-214不仅恢复了体外患病EPC的VEGF水平和血管生成活性，而且还进一步促进了小鼠缺血肢体的血流恢复。循环miR-214可能是CAD的一种新的生物标志物以及潜在的诊断工具。并且miR-214水平升高可用于预测CAD患者冠状动脉病变的存在和严重程度。
