Autonomic nervous regulation of the macrophage response in infarct healing

• Applicant: Privatdozent Dr. Sebastian Cremer
• Subject Area: Cardiology, Angiology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 326913253

Myocardial infarction elicits a rapid immune response leading to infiltration of the infarcted tissue by neutrophils and inflammatory monocytes. These cells are important for clearance of necrotic cells. They are mobilised from hematopoietic organs like bone marrow and spleen. The resolution of inflammation in the injured myocardium is of high importance for successful healing after myocardial infarction and is controlled by a distinct subpopulation of antiinflammatory monocytes. If the sequence of the two phases is disturbed, chronic heart failure develops, a disease with high mortality and lethality. Preliminary results show that the autonomic nervous system regulates the production of monocytes in bone marrow and spleen by signalling via the beta3-adrenoreceptor. In addition, increased activity of the sympathetic nervous system in bone marrow was documented after myocardial infarction. Based on this data the hypothesis that the autonomous nervous system controls the innate immune response and that unbalanced activity of the autonomous nervous system impedes resolution of the inflammatory response within myocardium after MI will be tested. With the help of different mouse models and imaging techniques the influence of the sympathetic and parasympathetic nervous system on haematopoiesis in bone marrow and spleen will be dissected. In a next step, the migration and recruitment of myeloid cells in the infarct tissue will be analysed. This will answer the question whether the autonomous nervous system regulates the biphasic immune response after MI. The anticipated results are of high importance from a translational point of view, as many of the receptors analysed can evolve as new targets for treatment of patients with myocardial infarction.

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