联合OCT研究血流紊乱调控EndMT/ROS正反馈环路在斑块侵蚀形成中的作用机制

斑块侵蚀继发血栓形成是急性心肌梗死（AMI）的重要原因。尽管病理研究证实其富含透明质酸、胶原等特征性细胞外基质（ECM），并伴有内皮细胞凋亡、剥脱，但具体形成机制仍未阐明，针对性临床防治面临瓶颈。我们前期应用高分辨率光学相干断层成像技术（OCT）在大样本AMI患者中原位诊断斑块侵蚀并证实靠近血管分支分布是其最强的独立预测因子，提示局部血流紊乱与斑块侵蚀形成密切相关。课题组进一步发现，内皮-间充质转化（EndMT）是连接流体紊乱、内皮细胞功能转变和特征性ECM表达的核心环节，且活性氧簇（ROS）可协同促进内皮细胞凋亡、剥脱。据此我们提出：局部血流紊乱调控EndMT/ROS正反馈环路是斑块侵蚀形成的重要机制。本项目联合OCT和分子生物学技术，利用体外流体系统模拟和基因修饰动物模型，从细胞、在体成像和原位诊断、病理等水平深入剖析上述机制在斑块侵蚀形成中的作用，为斑块侵蚀的临床防治提供新的思路。

Plaque erosion with subsequent thrombosis is an important cause of acute myocardial infarction (AMI). Although pathological studies have confirmed that it is rich in characteristic extracellular matrix (ECM) such as hyaluronic acid and collagen, and accompanied by apoptosis and detachment of superficial endothelial cells, the specific mechanism for the formation of plaque erosion has not been fully elucidated, and targeted clinical prevention and treatment faces bottlenecks. In our previous work, we applied high-resolution intravascular optical coherence tomography (OCT) to diagnose plaque erosion in situ in large sample AMI patients and demonstrated that the nearby bifurcation location is the strongest independent predictor of plaque erosion, suggesting that local disturbed blood flow is closely related to the formation of plaque erosion. Our research team further found that endothelial to mesenchymal transition (EndMT) is the core link connecting fluid disturbance, endothelial cell function transformation and characteristic ECM expression, and reactive oxygen species (ROS) can synergistically promote endothelial cell apoptosis and detachment. Therefore, we proposed that local disturbed blood flow regulating EndMT/ROS positive feedback loop is an important mechanism for the formation of plaque erosion. This project combines OCT and molecular biology technology, and uses in vitro fluid system and genetically modified animal model to deeply reveal the role of the above mechanism in the formation of plaque erosion from the levels of cell, in-vivo imaging and in situ diagnosis, to pathology. It is reasonable to speculate that the current project will provide novel ideas for the clinical prevention and treatment of plaque erosion.