Enhancing epicardial EMT to repair the heart

Dronkers, E. (2023)

Doctoral Thesis

Since the adult heart has minimal capacity to repair itself, myocardial infarction often leads to pathological remodeling and ultimately to the development of fatal heart failure. Upon ischemic injury, the epicardium, the outer layer of the heart which is essential for cardiac development, becomes re-activated and displays reparative potential. In this process, epicardial epithelial-to-mesenchymal transition (epiMT) is an essential step. We hypothesize that the reparative capacity of the heart can be improved by enhancing the participation of the epicardium to cardiac repair, particularly by stimulating the occurrence of epiMT. Therefore, the aim of my thesis is to find ways to boost epiMT in the injured heart. In this thesis, we describe a cell culture model which allows us to study epiMT. Using this model, we identify novel epiMT regulators. Because EMT is also involved in pathological remodeling, application of an epiMT stimulator should be transient and local. Therefore, we describe a method to locally administer these factors to the injured mouse heart.

• Epicardium
• Cardiac development
• Cardiac repair
• EMT
• Epithelial to Mesenchymal Transition
• Primary Cell Culture

• All authors: Dronkers, E.
• Supervisor: Goumans, M.J.T.H.
• Co-supervisor: Smits, A.M.
• Committee: Dijke, P. ten; Chuva de Sousa Lopes, S.M.; Dankers, P.Y.W.; Hoff, M.J.B. van den
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-02-02
• ISBN (print): 9789464587913
• Sponsorship: Hartstichting