The role of circulating miRNAs in diagnosis of acute myocardial infarction and the pathological significance
作者单位：Department of Cardiovascular SurgeryGuangdong Cardiovascular InstituteGuangdong General HospitalGuangdong Academy of Medical Sciences Department of CardiologyXiangya HospitalCentral South University Center for Vascular Biology and InflammationCardiovascular DivisionDepartment of MedicineBrigham and Women's HospitalHarvard Medical School Department of Gynecology and obstetricsXiangya 3rd HospitalCentral South University Department of PharmacologySchool of Pharmaceutical SciencesCentral South University
会议名称：《第十一届全国免疫学学术大会》
会议日期：2016年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：cardiomyocytes damage circulating miRNAs AMI pathological new therapeutic approach
摘 要：Objectives: We aimed to explore the diagnostic value of circulating miRNAs(miR-149, miR-208 b, miR-378, miR-424, miR-499 and miR-765) in AMI patients, and protective role of miR-208 b or miR-378 or metoprolol during H/R injury in H9c2 cell with their underlying mechanisms. Methods: 205 AMI patients and 85 healthy subjects, twelve week-old C57BL/6 mice AMI and H9c2 cells were included in this study. Total RNA was isolated from plasma and cardiac cell with TRIzol reagent. Circulating miRNAs levels were measured by quantitative real-time polymerase chain reaction. Results: We found that miR-208 b, miR-499 and miR-765 levels were significantly up-regulated by 9.6 fold, 5.2 fold, and 5.1 fold in AMI patients compared with healthy subjects(p0.001). Plasma miR-149, miR-378 and miR-424 levels were markedly downregulated by 5.5 fold, 4.9 fold and 5 fold in AMI patients compared with controls(p0.001). Plasma levels of these miRNAs were returned towards normal at 96 h after PCI(p0.001). We also found that plasma miR-208 b, miR-499 and miR-765 levels were significantly elevated by 11.5 fold, 3.9 fold, and 4.7 fold, while miR-149, miR-378 and miR-424 levels were noticeably decreased by 3.7 fold, 4.1 fold and 3.8 fold in Mice AMI compared with controls(p0.001). The ROC curves of plasma miR-208 b, miR-499, miR-765, miR-149, miR-378 and miR-424 represented a strong discrimination between AMI patients and healthy subjects, with an area under curve(AUC) of 0.974, 0.971, 0.965, 0.963 0.969 and 0.973, respectively. Conclusions: Our findings suggested that miR-208 b, miR-499, miR-765, miR-149, miR-378, miR-424 may be used as a novel and sensitive diagnostic biomarker for AMI patients. Inhibition of miR-208 b and overexpression of miR-378 were effectively protected cardiomyocyte damage during H/R injury through their potential targets NLK and TRAF6, represents a new therapeutic approach for ischemic heart disease. Furthermore, metoprolol protected cardiomyocytes damage against H/R in