基于影像学和分子生物学探究miR-318通过激活Hippo信号通路调控心肌梗死的机制

Myocardial infarction (MI) is a type of very serious ischemic heart disease. MI is mainly due to myocardial necrosis caused by coronary ischemia and hypoxia. MI has the characteristics of acute onset, high mortality and disability, and has become a threat to human health. However, the mechanism of MI pathogenesis still remains unclear. In preliminary experiment, we employed cardiac magnetic resonance imaging (CMR) to identify three MI patients, and extracted exosomes from the infarcted and non-infarcted tissues. The following miRNA-seq analyses revealed that miR-318 was highly expressed in the infarcted exosomes. Further in vivo experiments demonstrated that miR-318 activates the Hippo signaling pathway to reduce organ size. Bioinformatics analysis showed that YAP is a potential target for miR-318. Based on these data, we propose the hypothesis that the infarcted cell secretes miR-318-containing exosomes, in turn, the miR-318 activates the Hippo pathway through targeting YAP in infract marginal cells, culminating in cell death and promoting adverse ventricular remodeling. This project intends to combine imaging and molecular biology methods to elucidate the mechanism of miR-318 regulating myocardial infarction, and to explore the relationship between miR-318 expression level and infarct size. This study will provide theoretical guidance for the diagnosis and clinical treatment of myocardial infarction.

心肌梗死（MI）是一类非常严重的缺血性心脏病，主要指由冠状动脉缺血缺氧引起的心肌坏死。MI具有起病急，致死致残率高等特点，已成为威胁人类健康的原因。但是MI发病机理至今仍不清楚。前期，通过心脏核磁共振（CMR）筛选出三例MI病人，提取梗死区和非梗死区内的外泌体，进行miRNA-seq分析，发现miR-318在梗死区外泌体中高表达。进一步体内实验发现miR-318激活Hippo信号通路，减小器官面积。生物信息学分析显示，YAP是miR-318的潜在靶点。基于此，我们提出假说，MI病人梗死区细胞分泌携带miR-318的外泌体，miR-318靶向梗死边缘细胞的YAP，激活Hippo信号通路，诱导边缘区细胞死亡，促进不良心室重构。本项目拟结合影像学和分子生物学手段，阐明miR-318调控心肌梗死的机制，探究miR-318表达量与梗死面积之间的关联，为心肌梗死的诊断和临床治疗提供理论指导。

心肌梗死（Myocardial infarction，MI）是一类非常严重的缺血性心脏病，主要指由冠状动脉缺血缺氧引起的心肌坏死；MI具有起病急，致死致残率高等特点，已成为威胁人类健康的原因；但是MI发病机理至今仍不清楚。该项目对心肌梗死后心室重构过程中的变化进行了影像学、生物标记物与病理学关系的探讨。CMR-TT技术通过测量心肌应变及其衍生参数，实现对心肌运动功能和同步性的评估，从而有助于心肌梗死的程度的检测和识别心肌梗死后左室重塑，能更敏感地反映心脏早期受损，可重复性高，具有较好的临床应用前景。由细胞外泌体介导的miR-130a-3p直接针对ATG16L1可减轻心肌I/R损伤，为心肌I/R损伤提供新的治疗靶点。葡萄糖修饰的金纳米颗粒成功地标记了MSC来源的外泌体，这些标记的外泌体的PET-CT成像表明，心肌注射后MSC-Exo在心肌梗死区域保留了长达24小时，提示其在改善梗死后心功能方面的作用。结合影像学和分子生物学手段，能够更好的为心肌梗死的诊断和临床治疗提供理论指导。