Signaltransduction of aldosterone synthase (CYP11B2) during atrial fibrillation

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The requested project aims to identify the underlying mechanism of the aldosterone synthase (CYP11B2) mediated signal transduction of structural remodeling, especially of atrial fibrosis during atrial fibrillation, the most common arrhythmia. Samples of left atrial myocardium from patients with atrial fibrillation and sinus rhythm, cultured primary cardiac cells and transgenic mice with atrial fibrillation will be studied to identify new approaches of preventive interventions and to characterize mediators of the signal transduction of atrial remodeling. Specifically the following aims will be addressed.1) Characterization of CYP11B2 signal transduction in left atrial myocardium from patients with atrial fibrillation and sinus rhythm2) Functional characterization of the effects of CYP11B2-inhibition on the pro-fibrotic signal transduction in cardiac fibroblasts and myocytes3) Characterization of the new identified modulation of CYP11B2 by torasemid in vivo4) Functional and electrophysiological