房颤是一种衰老相关性疾病，我们在研究抗衰老基因Sesns在房颤中保护作用时，发现房颤时GATA-4/NF-κB-RelA通路激活，并且关注到GATA-4/NF-κB-RelA能通过选择性自噬促进细胞老化和纤维化。因此提出假设：“GATA-4/NF-κB-RelA通路过度激活，可能通过启动和维持SASP表达，促进衰老和纤维化，引起心房结构重构；通过降低Na+离子流，引起心房电重构，促进房颤的发生发展”。为验证假说，本课题将研究：①在HL-1房颤细胞模型上证实GATA-4/NF-κB-RelA在房颤电和结构重构中的作用；②在心房成纤维细胞中证实GATA-4/NF-κB-RelA在心房纤维化中的作用；③在房颤犬模型上证实GATA-4/NF-κB-RelA对心房电和结构重构的影响。本课题将阐明GATA-4/NF-κB-RelA通路在房颤重构中的作用及相关机制，为房颤防治提供新的研究方向和治疗靶点。

It has been known that atrial fibrillation (AF) is closely related to aging，We studied the protective effects of anti-aging gene Sesns in atrial fibrillation，and found that GATA-4/NF-κB-RelA pathway was activated，and noted that GATA-4/NF-κB-RelA can promote cell aging and fibrosis by selectiveautophagy. Therefore，GATA-4 are supposed as a cirtical factor, who paiticipates in atrial structural remodeling by promote cell aging and fibrosis through NF-κB-RelA signals and promotes electrical remolding by decrease Na+ and therefore results in AF incidence and persistence. To validate the hypothesis, we will investigate the followings: ① GATA-4/NF-κB-RelA will promote atrial electrical and structural remodeling in inpaced HL-1 atrial cells；② GATA-4 will promote fibroblasts activation by NF-κB-RelA/SASP signals in atrial fibroblast cells；③ GATA-4/NF-κB-RelA will promote electrical and structural remolding in dogs with chronic AF. This investigation will clarify the role of GATA-4/NF-κB-RelA signals and its related mechanism in AF remolding.Thus, we will provide novelty means to prevent and treat AF in the future.