Epicardial signal modulation in cardiac diseases

心脏的外层，心外膜，与心肌和冠状动脉相通。在动物实验中，心肌损伤后，心外膜细胞发生“上皮细胞向间充质细胞转化（EMT）”。随后，EMT细胞通过代谢、炎症和其他细胞机制迁移并与冠状动脉和心肌相互作用。虽然心外膜层在胚胎和动物心肌损伤后的作用已被充分了解，但其在冠状动脉疾病患者中的作用尚不清楚。心外膜层是否在维持左心室功能中起积极作用，需要进一步研究。在这个项目中，我的目标是在单核RNA的基础上，将冠心病患者的心外膜与非冠心病患者进行比较，并了解冠心病患者和左心室射血分数保留或降低的差异。这种方法的应用可以生成心外膜在我们患者群体中的作用的高分辨率图像。可以显示潜在的代谢、炎症和细胞变化。单核RNA分析之后将进行几项体外试验，以验证结果并了解心外膜的功能影响。心外膜-心肌相互作用的广泛图像的生成可以帮助在该领域找到新的治疗靶点。慕尼黑德国心脏中心提供了一个优秀的基础设施，可以快速获得结果，并将我的发现转化为这个项目。

The outer layer of the heart, the epicardium, communicates with the myocardium and coronary arteries. After myocardial injury, epicardial cells perform “epithelial to mesenchymal transitioning (EMT)” in animal studies. Subsequently, EMT cells migrate and interact with coronary arteries and the myocardium via metabolic, inflammatory and other cellular mechanisms. While the role of the epicardial layer is well understood in embryos and after myocardial injury in animals, less is known about its role in patients with coronary artery disease. Wether or not the epicardial layer plays an active role in preserving left ventricular function, needs to be investigated. Within this project, I aim to characterize the epicardium of patients with coronary artery disease (CAD) in comparison to patients without CAD on a single nuclei RNA basis and understand differences in patients with CAD and preserved or reduced left ventricular ejection fraction. The application of this method allows the generation of a high resolution picture of the role of the epicardium in our patient population. Potential metabolic, inflammatory and cellular changes can be displayed. Single nuclei RNA analysis will be followed by several in vitro assays to validate the results and understand the functional impact of the epicardium. The generation of a broad picture of the epicardial-myocardial interactions can help to find new therapeutic targets within the field. The German Heart Center Munich provides an excellent infrastructure to enable fast results and translate my findings within this projects.