心房电重构和结构重构是房颤发生发展的关键环节。研究表明核内溴结构蛋白4（BRD4）通过调控炎症、细胞周期、纤维化等过程参与到心血管疾病的发病机制中。但迄今，关于BRD4在房颤病理发生中的作用还未见报道。我们的预实验发现：1）房颤患者心房肌标本中BRD4表达明显高于窦律患者；2）Ang-II诱导的小鼠心房纤维化模型的心房肌中BRD4亦明显升高；3）BRD4抑制剂JQ1可逆转与房颤相关的电生理改变；4）在HL-1心房肌细胞系中过表达BRD4后表达谱芯片发现BRD4调控了心房肌细胞钙稳态相关基因CACNA1C和纤维化相关基因COL1A1、COL3A1，提示BRD4深度参与心房电重构与结构重构。据此假设BRD4通过介导电重构与结构重构的相关基因表达来发挥促房颤作用。本课题拟在分子、细胞、转基因小鼠及临床标本等水平上探讨BRD4在房颤中的作用，从而为临床治疗房颤提供新的作用靶点。

Atrial electrical remodeling and structural reconstruction are the key links in the development of atrial fibrillation. Studies have shown that Bromodomain containing protein 4 (BRD4) participates in the pathogenesis of cardiovascular disease by regulating inflammation, cell cycle, and fibrosis. But so far, the role of BRD4 in the pathogenesis of atrial fibrillation has not been investigated. We found in preliminary experiments: 1) BRD4 was significantly up-regulated in the atrial specimens incised surgically from patients with atrial fibrillation than that from patients with sinus rhythm; 2) BRD4 was also significantly elevated in mouse fibrotic atrial specimens induced by Ang-II; 3) The BRD4 inhibitor JQ1 can reverse the electrophysiological changes associated with atrial fibrillation; 4) A microarray on the HL-1 atrial cell line overexpressing BRD4 found out that calcium dynamics-related gene CACNA1C and profibrotic genes COL1A1 and COL3A1 are on the list of the EDGs, indicating that BRD4 is deeply involved in the atrial remodeling, both electrical and structural. We thus hypothesize that BRD4 promotes atrial fibrillation through regulations of above gene expressions. This study aims to explore the detail role of BRD4 in atrial remodeling at the levels of molecular, cellular, transgenic mice, and clinical specimens, thereby to provide a new target for the clinical treatment of atrial fibrillation.