房颤（Atrial fibrillation，AF）是一种老年病，随着我国人口的老龄化，AF患者逐年增加，但治疗效果仍不理想，其发病机制值得深入研究。心肌细胞衰老参与AF的病理过程，衰老的心房肌细胞可出现多种离子流改变，导致心房电重塑，但机制不明；我们的前期研究显示，辅转录激活因子和乙酰转移酶p300和其下游效应子Ahnak1在老龄AF和窦性患者左心房中表达均明显升高；而近期有研究发现心肌细胞中Ahnak1可通过与Cavβ2相互作用，参与ICa,L的调控；另外，随着年龄的增加，人骨骼肌中Ahnak表达增加，提示其参与衰老；因此本研究中我们拟在人体心房组织标本，心肌特异性敲除p300和衰老小鼠模型以及体外培养的心房肌细胞中，观察p300是否通过上调Ahnak1，激活其下游通路，参与衰老以及衰老相关的ICa,L下调，导致心房电重塑，以进一步阐明衰老导致AF的病理机制。

Atrial fibrillation (AF) is a kind of aging disease, its incidence increased with age. With the aging of the population, patients with AF in China will increase year by year, and the treatment of AF is still far from idea, especially for elderly patients; The aging of cardiomyocytes is involved in the pathological process of many cardiovascular diseases including AF; There are a variety of ion current changes in the aging atrial myocytes, which will lead to AF electrical remodeling, but its mechanism has not been elucidated; Our previous studies have shown that the expression of co-transcriptional activators and acetyltransferase p300 and its downstream signal Ahnak1 were increased in left atrial tissues from the aging patients with AF and sinus rhythm than in young patients. Ahnak1 is involved in the regulation of ICa,L by interacting with Cavβ2, and the over-expression of Ahnak1 will downregulate the Cyclin and lead to aging; So in this study we will investigate if p300 is involved in the aging of atrial myocytes and aging-related atrial electrical remodeling through the upregulation of Ahnak1, and subsequent senescence and Cavβ2-mediated inhibition of ICa,L, in human tissues, p300 knockout mice and aging mice and in vitro cultured atiral myocytes. The results will help us to elucidate the pathological mechanism of AF caused by aging.