Epicardial signal modulation in cardiac diseases

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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.