The scientists want to test the hypothesis that macrophages - a type of immune cell - play a key role in atrial fibrillation. A paper published in Cell in 2017 provided a promising clue: in this paper, the American project partners led by Matthias Nahrendorf with Munich participation showed that macrophages support electrical signal transmission in the heart. In 2023, a Science article was published which proved that macrophages appear more frequently in atrial fibrillation.
A new understanding of atrial fibrillation and therapies based on this understanding are urgently needed. It is expected that more than 30 million people in the USA and Europe will suffer from atrial fibrillation by 2050, as the main risk factors such as high blood pressure, diabetes, obesity and heart failure increase. Atrial fibrillation significantly increases the risk of stroke and heart failure.
However, the current treatment options are limited. Medication often has undesirable side effects, ablation therapies are only successful in half of patients and can lead to complications. Relapses after treatment are common, especially in patients with enlarged and scarred atria. There is currently no safe and effective method to prevent relapses of atrial fibrillation.
Large animal model from the DZHK site in Munich
‘The special thing about this project is that, for the first time, interdisciplinary experts are working together to systematically research the immunological processes involved in atrial fibrillation,’ says European project coordinator Stefan Kääb, a cardiologist and scientist at LMU Hospital. He himself is a rhythmologist, i.e. a specialist in the electrical processes in the heart.
The American partners are contributing their expertise in genetics and the molecular mechanisms of atrial fibrillation. Immunologists and oncologists are coming from France. Dutch colleagues are providing a biobank of heart tissue. The DZHK site in Munich is contributing a large animal model developed there to the collaboration, which combines the typical risk factors of atrial fibrillation patients: obesity, high blood pressure and mitral valve insufficiency.
Inflammations trigger atrial fibrillation
Macrophages play an important role in inflammation and can contribute to the increased formation of scar tissue in the heart, which increases the risk of atrial fibrillation. ‘It is also known that there are inflammatory triggers for atrial fibrillation, for example that it occurs more frequently after infections. However, the cells and mechanisms involved have never been systematically investigated,’ says Kääb.
The international team now wants to find out how macrophages influence the electrical conduction system in the heart and contribute to the development of atrial fibrillation. To this end, they are investigating the role of these cells in human heart tissue and in animal models. Their aim is to develop new therapeutic approaches that target macrophages in order to prevent or treat atrial fibrillation.
The research project is supported by the renowned Leducq Foundation, which is dedicated to promoting innovative scientific approaches to improving heart health within the framework of transatlantic projects.
Project title: Immune targets for the treatment of atrial fibrillation
Project partners:
- North American coordinator: Matthias Nahrendorf, Harvard Medical School, Boston
- European Coordinator: Stefan Kääb, Ludwig-Maximilians-Universität Munich
- USA: Patrick T. Ellinor, Kamila Naxerova, Harvard Medical School, Boston
- Europe: Sebastian Clauss, Ludwig-Maximilians-University Munich | Florent Ginhoux, INSERM, Villejuif, France | Ulrich Schotten, Maastricht University, Netherlands
Publications:
Hulsmans M, et al., Recruited macrophages elicit atrial fibrillation. Science 381,231-239 (2023). doi:10.1126/science.abq3061
Hulsmans M, Clauss S, Xiao L, et al. Macrophages Facilitate Electrical Conduction in the Heart. Cell. 2017;169(3):510-522.e20. doi:10.1016/j.cell.2017.03.050
