Remodelling of the autonomic nervous system in heart disease
Team: Karin Ziegler, Sandro Meunier, Pauline Pichler, Luisa Gündel, Sabine Brummer, Urszula Kremser, Anton Bomhard, Julia Auerswald, Reginald van der Kwast, Andrea Lang
The autonomic nervous system tightly innervates and controls the heart. Hereby, two supersystems, the parasympathetic and sympathetic nervous system, modulate divergent cardiac functions. It is well established that continuous overactivation of the sympathetic nervous system is a key pathophysiological factor that further promotes and aggravates cardiac disease progression.
The superior cervical ganglion (SCG), an important neuronal relay of the sympathetic nervous system, undergoes extensive structural remodelling in chronic cardiac stress. We have shown that SCG remodelling shares hallmarks of inflammation, with macrophages critically contributing to the phenotype (Ziegler et al., 2018). Most recently, we have, for the first time, revealed that the neuronal circuit between the SCG, the pineal gland and the myocardium impacts on the cardiac function and adverse remodelling of the heart (manuscript in revision).
The mechanisms which underly the inflammatory phenotype of the SCG, and the role of intercellular communication between cell types (e. g. immune cells), are just beginning to be resolved. We aim to systematically analyse neuronal remodelling in cardiac disease by state-of-the-art methodology such as single nuclei RNA sequencing, spatial RNA sequencing and tissue clearing. By identifying the molecular key mechanisms, we further aim to therapeutically modulate them in order to develop new treatment strategies for cardiac disease.
Ziegler, K. a. et al. Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice. Cardiovasc. Res. 114, 291–299 (2018).
Spatial RNA sequencing of the superior cervical ganglion (SCG)