The role of cardiac glial cells in the arrhythmic heart

• Applicant: Dr. Katharina Scherschel
• Subject Area: Cardiology, Angiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 525357558

Sudden cardiac death induced by ventricular arrhythmias is estimated to account for one quarter of all cardiovascular deaths worldwide. Despite the high number of fatalities, current approaches for pharmacological and interventional treatment are insufficient with limited success rates. Genesis and maintenance of cardiac arrhythmias have been connected to the autonomic nervous system. Neuromodulation – in form of stimulation and denervation of cardiac autonomic structures – is therefore under investigation for the treatment of arrhythmias, but current approaches omit the cellular interactions that contribute to normal nerve physiology: Glial cells are indispensable for neuronal function in the central and peripheral nervous system, but their role in the heart is vastly understudied. Our preliminary work indicates that glia in the heart accompany cardiac autonomic structures up to the smallest unit – the neuro-cardiac junction – and release neurotrophic factors upon myocardial nerve damage in mice and humans. Very few, but groundbreaking studies from others highlight a role for glia cells for maintenance of normal heart rhythm. We hypothesize that cardiac glia modulate electrophysiology of the heart via the autonomic nervous system. The goals of the current project are therefore to (1) perform a deep phenotyping of cardiac glia in healthy mice, (2) identify the impact of glial cells on cardiac electrophysiology in the healthy mouse heart and (3) determine the role of cardiac glia in neuronal remodeling processes after myocardial injury. For this, we will use transgenic mouse models that allow studying cardiac glial cells and manipulating their function. We will employ immunohistochemical, molecular biological and electrophysiological approaches for characterization and findings will be validated in human cardiac tissue. A model of myocardial infarction will allow addressing glial responses in the pathophysiological setting. In summary, this project will bring light into glia cells as an overlooked cell population in the heart and might identify cardiac glia as novel targets for the treatment of ventricular arrhythmias in future.

• DFG Programme: Research Grants