斑块破裂继发血栓形成是急性心肌梗死（AMI）事件链的上游和核心环节，如能早期识别并及时治疗，可很大程度避免后续心肌坏死。在NSFC项目支持下，我们前期和预实验发现循环miRNAs可作为早期诊断斑块破裂的潜在标志物及抑制血栓形成的新靶点。为进一步证实上述发现，本项目拟开展：1、利用PCI时球囊扩张造成斑块损伤模拟人体斑块破裂，并应用AMI患者发生斑块破裂但尚未心肌坏死阶段的血液标本，通过高通量筛查、初步验证和扩大验证，确定斑块破裂后表达水平变化的循环miRNAs，并探讨其早期诊断斑块破裂的价值。2、通过生物信息学分析获得可能调控斑块破裂后血栓形成的候选循环miRNAs，在上调/下调候选miRNAs的细胞上、敲除/敲入候选miRNAs的apoE-/-小鼠中，确定候选miRNAs调控斑块破裂后血栓形成的作用与机制。最终明确可早期诊断斑块破裂的循环miRNAs标志物，并为AMI抗栓治疗提供新靶点。

Acute myocardial infarction (AMI) is mainly triggered by plaque rupture and subsequently thrombus formation. The early identification and treatment of AMI could significantly alleviate myocardial necrosis. Under the support of National Natural Science Foundation of China, our previously study revealed that circulating microRNAs (miRNAs) may serve as potential early diagnosis biomarkers of plaque rupture and may be involved in the regulation of thrombosis. To further demonstrate the key role of circulating miRNAs in the early diagnosis of plaque rupture and the regulation of thrombosis, we will carry out the following studies: 1. We use percutaneous coronary intervention-induced plaque injury to mimic plaque rupture in patients with coronary heart disease and used plasma from AMI patients before myocardial necrosis, to assess the possibility of circulating miRNAs as biomarkers of plaque rupture, which are proved by profiling-replication-validation model. 2. We obtain the thrombosis-related miRNAs by bioinformatics analysis and determine their role by gain of function and loss of function in cells and apoE-/- mice. This project will present miRNAs biomarkers for the early diagonosis of plaque rupture and new treatment target of AMI.