miRNA in peripheral and coronary serum of CAD and acute MI patients

Background: We aimed to identify circulating miRNA associated with chronic coronary artery disease (CAD) and myocardial infarction (MI) in peripheral blood vessels and coronary arteries proximal to an occluded culprit area. Methods: Patients having chronic CAD, acute MI either with or without ST segment elevation (STEMI and NSTEMI, respectively), and control patients with no previous or current CAD, were recruited to the study. Blood samples were collected during coronary catheterization procedure from the peripheral and from the culprit coronary artery. Serum miRNA was sequenced, and miRNA identified as differentially expressed was validated by quantitative-real-time PCR. Results: Sequencing analysis revealed miR-483-5p as differentially expressed in STEMI patients versus controls. Further qPCR experiment demonstrated a significant downregulation of miR-483-5p in peripheral samples of CAD and MI patients compared with controls (1.1 vs.2.6, respectively). In coronary samples, miR-483-5p was reduced only in chronic CAD, whereas its expression in MI patients was similar to controls. A ROC analysis for association of peripheral serum miR-483-5p with chronic CAD demonstrated an area under the curve of 0.722. Conclusion: miR-483-5p is differentially expressed in chronic CAD and MI and has local effects in culprit artery, suggesting it as an important player in CAD and a potential biomarker.背景：本研究旨在在外周血管以及闭塞责任病灶区域附近的冠状动脉中，筛选与慢性冠状动脉疾病（chronic coronary artery disease, CAD）、心肌梗死（myocardial infarction, MI）相关的循环微小核糖核酸（miRNA）。方法：本研究纳入慢性冠状动脉疾病患者、伴或不伴ST段抬高的急性心肌梗死患者（分别为ST段抬高型心肌梗死（STEMI）与非ST段抬高型心肌梗死（NSTEMI）），以及无既往或当前冠状动脉疾病病史的对照患者。在冠状动脉造影术操作过程中，采集受试者的外周血以及责任冠状动脉的血液样本。对血清miRNA进行测序，筛选出的差异表达miRNA通过实时定量PCR（quantitative-real-time PCR）进行验证。结果：测序分析显示，与对照组相比，STEMI患者的miR-483-5p表达存在显著差异。后续实时定量PCR实验证实，与对照组相比，CAD及MI患者外周血样本中的miR-483-5p表达显著下调（相对表达量分别为1.1与2.6）。在冠状动脉样本中，miR-483-5p仅在慢性CAD患者中表达下调，MI患者的miR-483-5p表达水平与对照组无显著差异。针对外周血清miR-483-5p与慢性CAD的相关性进行受试者工作特征曲线（Receiver Operating Characteristic, ROC）分析，结果显示曲线下面积为0.722。结论：miR-483-5p在慢性CAD及MI中存在差异表达，并在责任冠状动脉中发挥局部调控作用，提示其在冠状动脉疾病发病过程中扮演重要角色，同时具备成为潜在生物标志物的潜力。