Chen Jiuling, Sheng Siqi, Zhang Jinhui, Li Yuchen, Jiang Tingting, Jiang Xiaohui, Li Jiahao, Lv Lin, Wang Zhiqi, Wei Yongkang, Fang Ning, Zhang Song, Yao Hong, Dong Yanghong, Xue Zheng, Dong Zengxiang, Liang Zhaoguang
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, #23 Youzheng Street, Harbin, Heilongjiang Province 150001, China.
The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, The First Affiliated Hospital of Harbin Medical University, #23 Youzheng Street, Harbin, Heilongjiang Province 150001, China.
Europace. 2025 Jul 1;27(7). doi: 10.1093/europace/euaf127.
Although many large-scale clinical studies have confirmed that depression is an independent risk factor for atrial fibrillation (AF), the underlying mechanism remains unclear. This study aimed to investigate the pathogenesis of depression-associated AF.
The chronic unpredictable mild stress model of depression was established. In this model, we observed a significant increase in AF inducibility. In order to explore its potential mechanism, we analysed the serum metabolomics of humans and rats and the protein metabolomics of atrial tissue in rats. The levels of N-palmitoyl glycine in different tissues were quantified using liquid chromatography-mass spectrometry. Both in vivo and in vitro experiments were performed to validate the proposed mechanisms. Electrophysiological changes in isolated hearts were evaluated using the Langendorff perfusion system and multi-channel electrical mapping. Our findings suggest that N-palmitoyl glycine secreted by the white matter acts as a key factor in depression-associated AF. Both in vivo and in vitro experiments revealed that N-palmitoyl glycine reduces autophagy and the synthesis of nebulin-related anchoring protein in atrial myocytes by up-regulating α1,2-mannosidase expression. These changes lead to the intercalated disc rupture, a critical event in the pathogenesis of AF.
This study demonstrates that N-palmitoyl glycine plays a crucial role in the development of AF in the context of depression. These findings provide potential therapeutic targets for the prevention and treatment of AF following depression.
尽管许多大规模临床研究已证实抑郁症是心房颤动（AF）的独立危险因素，但其潜在机制仍不清楚。本研究旨在探讨抑郁症相关心房颤动的发病机制。
建立抑郁症慢性不可预测轻度应激模型。在该模型中，我们观察到房颤诱导率显著增加。为了探究其潜在机制，我们分析了人和大鼠的血清代谢组学以及大鼠心房组织的蛋白质代谢组学。使用液相色谱 - 质谱法定量不同组织中N - 棕榈酰甘氨酸的水平。进行了体内和体外实验以验证所提出的机制。使用Langendorff灌注系统和多通道电标测评估离体心脏的电生理变化。我们的研究结果表明，白质分泌的N - 棕榈酰甘氨酸是抑郁症相关房颤的关键因素。体内和体外实验均表明，N - 棕榈酰甘氨酸通过上调α1,2 - 甘露糖苷酶表达来减少心房肌细胞中的自噬和nebulin相关锚定蛋白的合成。这些变化导致闰盘破裂，这是房颤发病机制中的关键事件。
本研究表明N - 棕榈酰甘氨酸在抑郁症背景下房颤的发生发展中起关键作用。这些发现为抑郁症后房颤的预防和治疗提供了潜在的治疗靶点。
