Modeling of the cardiac sympathetic nervous system and the contribution of epicardium-derived cells

Ge, Y. (2021)

Doctoral Thesis

The heart is innervated by the autonomic nervous system, which can be divided into sympathetic and parasympathetic parts. The balance between cardiac sympathetic and parasympathetic innervation is critical for maintaining normal cardiac function. After myocardial infarction, sympathetic hyperinnervation has been discovered in patients as well as in animal models, which has raised growing awareness in relation to arrhythmogenesis. However the mechanism is not clear yet. In this thesis, we hypothesize a role for epicardium-derived cells (EPDCs) in this process. In addition, we aimed to study ganglia remodeling after myocardial infarction. We explored: i) the role of EPDCs in promoting cardiac sympathetic re-/hyperinnervation after cardiac damage in vitro, ii) the impact of sex of EPDCs on cardiac innervation, iii) the generation of inducible proliferative human EPDCs (iEPDCs), iv) neuronal remodeling of superior cervical ganglia after myocardial infarction and v) the molecular signature of SCG revealed by single nucleus RNA sequencing.

• Cardiac autonomic nervous system
• Myocardial infarction
• Cardiac sympathetic innervation
• Superior cervical ganglion
• Carotid body
• Epicardium-derived cells
• Sex differences
• Neurotrophic factors
• Conditional immortalization
• Single nucleus RNA sequencing

• All authors: Ge, Y.
• Supervisor: Ruiter, M.C. de; Schalij, M.J.
• Co-supervisor: Jongbloed, M.R.M.
• Committee: Goumans, M.J.T.H.; Salvatori, D.; Bleys, R.L.A.W.; Gils, J.M .van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
• Date: 2021-12-15
• ISBN (print): 9789493270312