Linking functional microarchitecture of the myocardial infarction borderzone to arrhythmogenesis
The mortality associated with a heart attack has become quite low due to better treatment during this acute event. However, life-threatening rhythm disorders often develop in the following months and years for which treatment remains limited. Providing novel insights in the underlying mechanisms is the major aim of the proposed research. The proposal builds on the power of novel research tools to investigate why the border zone around the scar that formed after the heart attack is the source of such rhythm disorders. We use a pig model recapitulating the human disease progression after a heart attack. We map the precise areas in the border zone that trigger the rhythm disorders, recording the electrical events, and matching those with the detailed structure of these areas. Tissue samples are processed to explore which cell types are present that distinguish these areas, using advanced gene expression studies. We study how different cell types influence the function of the heart muscle cells that are the source of the abnormal electrical activity and rhythm disorders. We study in detail the influence of a cell type that is involved in scar formation, the myofibroblast, and define the signaling network between different cell types. The outcome of our study can refine current treatment as well as guide further studies exploring the potential to target the signaling uncovered by our work.