Laboratory of Cellular Optics II

Structural remodeling of the heart as occurring in the context of pressure overload and infarction is a well established cause of cardiac arrhythmias and mechanical dysfunction. The histopathology of structural remodeling is characterized by the appearance of myofibroblasts in the myocardium which critically contribute to fibrosis by excessive production of extracellular matrix proteins.
Apart from this pro-fibrotic effect, our group is investigating the hypothesis that myofibroblasts might additionally play an essential role in cardiac arrhythmogenesis by directly modifying cardiomyocyte electrophysiology. In support of this hypothesis, we found that cardiac myofibroblasts induce slow and discontinuous conduction as well as ectopic activity which, in combination, result in the precipitation of tachyarrhythmias in tissue engineered models of cardiac tissue. Presently, we conduct a detailed characterization of the molecular determinants of the arrhythmogenic effects of myofibroblasts on cardiomyocytes with the goal to unveil novel therapeutic targets for the treatment of both ventricular and atrial cardiac arrhythmias.