中国胸心血管外科临床杂志

中国胸心血管外科临床杂志

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黏着斑激酶介导信号通路在瓣膜性心房颤动心房纤维化中的研究

张培德 , 李飞 , 乔恩 , 王巍

中国医学科学院阜外医院 国家心血管病中心（北京 100037）

收稿日期: 2018-07-25;  修回日期:2018-09-21; 

基金项目: 国家自然科学基金青年基金（81600254）

通讯作者: 王巍, Email: drweiwang0728@hotmail.com

Focal adhesion kinase mediated signaling on atrial fibrosis in patients with valvular atrial fibrillation

ZHANG Peide , LI Fei , QIAO En , WANG Wei

Fuwai Hospital, China academy of medicine science, National Center for Cardiovascular Disease, Beijing, 100037, P.R.China

Corresponding Author: WANG Wei, Email: drweiwang0728@hotmail.com

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目的 探索 FAK 在瓣膜性心房颤动（房颤）患者纤维化心房中的变化，并对其介导的下游信号通路进行探究。 方法 共有 45 例二尖瓣疾病患者纳入本次研究，根据有无房颤分为瓣膜房颤组（VAF，AF>6 个月，25 例）和窦性心律组（SR，20 例）。术中获取心耳组织，分别进行组织学病理检测和蛋白免疫印迹。观察心房纤维化程度以及 FAK 及其下游通路在纤维化心肌中的变化。 结果 本研究揭示了瓣膜性房颤心房纤维化程度较高，细胞排列紊乱。通过探究 FAK 及下游通路的变化，发现房颤组成纤维细胞分化标志蛋白 α 平滑肌肌动蛋白（α-SMA）表达明显升高，FAK 及下游 AKT/S6K 通路蛋白表达均发生上调，而另一条信号通路 ERK1/2 信号通路未见明显变化。 结论 瓣膜性房颤心房纤维化是心房结构重塑的一个重要标志,胶原纤维的过度产生使心房肌细胞的连续性受到破坏，导致传导异常，为房颤发生发展提供了基质环境。粘着斑激酶及下游 AKT/S6K 信号通路在纤维化心肌中表达增加，可能参与心房纤维化进程之中，为其机制研究提供依据。

Objective To explore the changes of focal adhesion kinase(FAK) in the fibrotic atrium of patients with valvular atrial fibrillation and explore its downstream signaling pathways. Methods A total of 45 patients with mitral valve disease were included in this study and were divided into valvular atrial fibrillation (VAF, AF>6 months, 25 patients) and sinus rhythm group (SR, 20 patients) based on having atrial fibrillation or not. The atrial appendage tissue was obtained during the operation , histopathological examination and Western blotting were performed. The degree of atrial fibrosis and changes in FAK and its downstream pathways in fibrotic myocardium were observed. Results This study revealed a higher degree of atrial fibrosis in valvular atrial fibrillation and disordered cell arrangement. Expression of fibroblast differentiation marker alpha smooth muscle actin (α-SMA) was significantly increased in atrial fibrillation, and the expression of FAK and downstream AKT/S6K pathway proteins was up-regulated, while the other signal was observed, there was no significant change in ERK1/2 signaling pathway. Conclusion Atrial fibrosis in valvular atrial fibrillation is an important feature of atrial structural remodeling. We found overproduction of collagen fibers disrupted the continuity of atrial myocytes, leading to abnormal conduction and providing a matrix environment for the development of atrial fibrillation. The expression of focal adhesion kinase and downstream AKT/S6K signaling pathway in fibrotic myocardium may be involved in the process of atrial fibrosis, providing a basis for the study of its mechanism.

关键词: 瓣膜性房颤; 心房纤维化; 黏着斑激酶; 信号通路

Key words: Valvular atrial fibrillation; atrial fibrosis; focal adhesion kinase; signaling pathway

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