Autonomic nervous regulation of the macrophage response in infarct healing

• Applicant: Dr. Maximilian J. Schloss
• Subject Area: Cardiology, Angiology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 411719800

Cardiovascular diseases and especially myocardial infarction (MI) are the leading causes of death in Western countries. In the US, myocardial infarction happens every 25 seconds and 30 percent of the patients are under the age of 65. This syndrome continues to be lethal despite current guideline therapy. While the numbers of survivors have been increasing, they often face long-term disabilities; survival chances are particularly poor, if post-MI heart failure occurs. Emerging evidence indicates that the immediate post-MI recovery phase, particularly the cardiac wound healing processes in which macrophages play a crucial role, strongly determine a patient’s fate: if wound healing derails, infarct expansion and heart failure compromise the quality of life and survival. In order to achieve a high quality of cardiac wound healing, the extent of the inflammation needs to be scrupulously controlled. An imbalanced or exaggerated inflammatory milieu in the infarcted myocardium compromises infarct healing and leads to cardiac failure. The decision nodes that regulate systemic cellular supply and the paths that lead to the resolution of infarct inflammation are not yet completely understood.It has been observed that in patients with MI and heart failure, sympathetic nervous activity increases while vagus nerve activity decreases leading to a nerval imbalance. This affects patients’ mortality negatively. A possible explanation is that if the sympathetic nervous system activity continues to dominate in the second post ischemic phase, infarct healing may be compromised by immune cell oversupply, failed resolution and insufficient repair processes. Therefore, while previous studies show that the autonomic nervous system influences crucial pathophysiological processes after MI, our overall picture of these processes are rather incomplete. This project will test the overarching hypothesis that the autonomic nervous system interfaces with innate immunity and posits the autonomic nervous system as the regulator of the transition from inflammation to resolution. This research is important because the pathways and receptors involved in this process are not targeted by current MI therapy. The knowledge obtained through the novel data acquired in this project has the potential to dramatically change MI therapy and thereby improve the survival rates of MI patients and their quality of life.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Matthias Nahrendorf