Signaltransduction of aldosterone synthase (CYP11B2) during atrial fibrillation

所申请的项目旨在确定醛固酮合成酶（CYP11B2）介导的结构重构信号转导的潜在机制，特别是房颤（最常见的心律失常）期间的心房纤维化。我们将研究心房颤动和窦性心律患者的左心房心肌样本、培养的原代心肌细胞和心房颤动转基因小鼠，以确定预防干预的新方法，并表征心房重构的信号转导介质。具体而言，将讨论以下目标。1)心房颤动和窦性心律患者左心房心肌CYP11B2信号转导的研究2)抑制CYP11B2对心肌成纤维细胞和肌细胞促纤维化信号转导的影响的功能研究3)新发现的托拉塞米在体内调节CYP11B2的研究4)功能和电生理研究

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