The Role of ERBB4 in Atrial Electrophysiology and Atrial Fibrillation

项目摘要 房颤（AF）是卒中的主要原因，也是美国发病率和死亡率的主要原因。AF是 由于遗传和后天因素。全基因组关联研究已经将ERBB4确定为一种 AF的候选易感基因。获得性疾病，如衰老、高血压和心力衰竭， 已知在称为重构的过程中引起左心房（LA）的电和结构变化， 我们的数据显示房颤患者左心房ERBB 4水平降低。 显示ErbB4在心脏病小鼠模型中下调。研究ErbB4在心房肌细胞中的作用， 电发展和获得性AF机制，我们已经产生了小鼠模型， ErbB4在发育过程中表达或在成年期获得。这两个模型系统都显示出重要的 正确的ErbB4基因剂量在维持正常心房电生理中的依赖性。

PROJECT SUMMARY Atrial fibrillation (AF) is the leading cause of stroke and a major cause of morbidity and mortality in the US. AF is due to both inherited and acquired factors. Genome-wide association studies have identified ERBB4 as a candidate susceptibility gene for AF. Acquired conditions, such as aging, hypertension, and heart failure, are known to cause electrical and structural changes in the left atrium (LA) in a process known as remodeling that predisposes to AF. Our data show that left atrial ERBB4 levels are reduced in patients with AF. We have also shown that ErbB4 is downregulated in heart disease mouse models. To study the role of ErbB4 in both atrial electrical development and in acquired AF mechanisms, we have generated mouse models that have reduced ErbB4 expression during development or acquired during adulthood. Both model systems show an important dependency of correct ErbB4 gene dosage in the maintenance of normal atrial electrophysiology.