Cross-Talk of Cells in the Heart 2025 (University of Birmingham, UK) (2025) Proc Physiol Soc 66,
SA06
Research Symposium: Disease-in-a-dish models to understand the mechanisms of atrial fibrillation in cardiomyopathies
Katja Gehmlich1, Max Cumberland2, Ashwin Roy2, Andrew Holmes3, Davor Pavlovic2, Chris O'Shea4, Richard Steeds2
1 Cardiovascular Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham and Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford United Kingdom, 2Cardiovascular Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham United Kingdom, 3Department of Biomedical Sciences, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham United Kingdom, 4Cardiovascular Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham and Heart Rhythm Research Group, Division of Biomedical Sciences, Warwick Medical School, Clinical Sciences Research Laboratory United Kingdom
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Atrial fibrillation is a common phenomenon in patients affected by inherited cardiac diseases, called cardiomyopathies. The traditional view is that structural remodelling, i.e. atrial enlargement and fibrosis, are responsible for this, however, novel observations suggest that atrial fibrillation may precede overt structural remodelling.
To get detailed insights into drivers of pro-arrhythmic changes, we have developed ‘disease-in-a-dish’ models for cardiomyopathies, making use of human induced pluripotent stem cell derived atrial cells. Our electrophysiological characterisation, using patch clamp and optical mapping approaches, has identified intrinsic changes in the electrical properties of atrial cardiomyocytes carrying key cardiomyopathy-associated mutations. Moreover, using 3D co-culture systems of atrial cardiomyocytes and cardiac fibroblasts, we can demonstrate that cross-talk between atrial cardiomyocytes and fibroblasts leads to fibroblast activation, a key event in fibrosis.
In conclusion, our models systems confirm the pro-arrhythmic characteristics of atrial cardiomyocytes and further provide an understanding of their mechanisms.
Where applicable, experiments conform with Society ethical requirements.
