Signaltransduction of aldosterone synthase (CYP11B2) during atrial fibrillation

申请的项目旨在确定醛固酮合酶（CYP11B2）介导的结构重构信号转导的潜在机制，特别是房颤期间的心房纤维化，最常见的心律失常。将研究房颤和窦性心律患者的左心房心肌样品、培养的原代心脏细胞和房颤转基因小鼠，以确定预防性干预的新方法，并表征心房重构信号转导的介质。具体而言，将解决以下目标。1）房颤和窦性心律患者左心房心肌中CYP11 B2信号转导的表征2）CYP11 B2抑制对心脏成纤维细胞和肌细胞中促纤维化信号转导影响的功能表征3）托拉塞米体内新发现的CYP11 B2调节的表征4）功能和电生理学

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