Electrophysiological Functions of Macrophages are Involved in Atrial Fibrillation.

IF 0.5 4区医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS

Kardiologiya Pub Date : 2025-06-02 DOI:10.18087/cardio.2025.5.n2780

Jieqiong Wang, Wenjing Chen, Zewei Sun

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Abstract

Aim: Inflammation, in which macrophages play an important role as immune cells, is closely related to atrial fibrillation (AF). Recent studies have shown that macrophages participate electrical conduction in the heart, thus indicating that they have electrophysiological characteristics. However, whether the electrophysiology of macrophages is associated with AF or not remained unknown. Thus, we investigated the biological function changes in macrophages using patch-clamping after tachypacing to mimic AF.

Material and methods: Atrial myocytes and macrophages were cultured. RNA sequencing was performed to investigate the expression change of atrial myocytes after tachypacing. Patch-clamping was conducted to measure the change of APD and ICa,L in macrophages after tachypacing. Rapid atrial stimulation was performed to measure the AF incidence in macrophage-specific CX43 knockout mice.

Results: After tachypacing, the time required for 90% repolarization of the action potential and the ICa,L were reduced in macrophages. Furthermore, we found that tachypacing atrial myocytes led to the secretion of Wnt 7a, further inhibiting the expression of CACNA1C in macrophages. Moreover, the knockout of CX43 in macrophages decreased the incidence of AF in a mouse model of chronic inflammation.

Conclusion: The electrophysiology of macrophages is related to the development of AF and might be a potential therapeutic target for AF therapy. Prospects for the transfer of laboratory data to the clinic: 1) Regulation of macrophage electrophysiology might be a potential therapeutic target for atrial fibrillation (AF). 2) A Wnt 7a inhibitor could be used to decrease AF incidence. 3) Blocking the interaction between macrophages and atrial myocytes might be a potential therapeutic target for AF.

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巨噬细胞电生理功能参与心房颤动。

目的：炎症与心房颤动（AF）密切相关，其中巨噬细胞作为免疫细胞发挥着重要作用。近期研究表明，巨噬细胞参与心脏电传导，具有电生理特性。然而，巨噬细胞的电生理是否与房颤相关尚不清楚。因此，我们采用膜片夹紧法模拟心房颤动后巨噬细胞的生物学功能变化。材料和方法：心房肌细胞和巨噬细胞培养。采用RNA测序方法观察心房肌细胞在心动过速后的表达变化。采用patch -clamp法测定巨噬细胞速搏后APD和ICa，L的变化。采用快速心房刺激法测量巨噬细胞特异性CX43基因敲除小鼠心房颤动发生率。结果：速搏后巨噬细胞动作电位90%复极化所需时间及ICa、L均降低。此外，我们发现心房肌细胞过速导致Wnt 7a的分泌，进一步抑制巨噬细胞中CACNA1C的表达。此外，巨噬细胞中CX43的敲除降低了慢性炎症小鼠模型中AF的发生率。结论：巨噬细胞的电生理与房颤的发生有关，可能是房颤治疗的潜在靶点。实验室数据向临床转移的前景：1)调节巨噬细胞电生理可能是心房颤动（AF）的潜在治疗靶点。2) Wnt 7a抑制剂可降低AF发生率。3)阻断巨噬细胞与心房肌细胞的相互作用可能是心房颤动的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Kardiologiya 医学-心血管系统

CiteScore

1.70

自引率

20.00%

发文量

审稿时长

3-8 weeks

期刊介绍： “Kardiologiya” (Cardiology) is a monthly scientific, peer-reviewed journal committed to both basic cardiovascular medicine and practical aspects of cardiology. As the leader in its field, “Kardiologiya” provides original coverage of recent progress in cardiovascular medicine. We publish state-of-the-art articles integrating clinical and research activities in the fields of basic cardiovascular science and clinical cardiology, with a focus on emerging issues in cardiovascular disease. Our target audience spans a diversity of health care professionals and medical researchers working in cardiovascular medicine and related fields. The principal language of the Journal is Russian, an additional language – English (title, authors’ information, abstract, keywords). “Kardiologiya” is a peer-reviewed scientific journal. All articles are reviewed by scientists, who gained high international prestige in cardiovascular science and clinical cardiology. The Journal is currently cited and indexed in major Abstracting & Indexing databases: Web of Science, Medline and Scopus. The Journal''s primary objectives Contribute to raising the professional level of medical researchers, physicians and academic teachers. Present the results of current research and clinical observations, explore the effectiveness of drug and non-drug treatments of heart disease, inform about new diagnostic techniques; discuss current trends and new advancements in clinical cardiology, contribute to continuing medical education, inform readers about results of Russian and international scientific forums; Further improve the general quality of reviewing and editing of manuscripts submitted for publication; Provide the widest possible dissemination of the published articles, among the global scientific community; Extend distribution and indexing of scientific publications in major Abstracting & Indexing databases.