Ke Yuanjia, Cao Zhen, Wang Xuewen, Liu Dishiwen, Fu Yuntao, Chen Huiyu, Cheng Yanni, Guo Kexin, Li Yajia, Long Xiaojian, Yang Mei, Zhao Qingyan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China.
Can J Cardiol. 2025 Feb;41(2):195-209. doi: 10.1016/j.cjca.2024.08.266. Epub 2024 Aug 13.
The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of K3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing.
Part 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were co-cultured to explore the specific migratory mechanism of macrophages.
Depleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodelling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells was significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that K3.1 regulated CCL2 secretion through the p65/STAT3 signalling pathway.
Inhibiting myocardial K3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which K3.1 regulates CCL2 may be related to the p65/STAT3 signalling pathway.
局部心外膜脂肪组织（EAT）巨噬细胞与心房颤动（AF）之间的关系尚不清楚。本研究旨在探讨K3.1在快速起搏过程中巨噬细胞从EAT迁移至相邻心房组织中的作用。
第一部分：18只比格犬随机分为假手术组、起搏组和起搏+氯膦酸盐脂质体（CL）组。第二部分：18只比格犬随机分为假手术组、起搏组和起搏+TRAM-34组。将HL-1细胞与RAW264.7细胞共培养以探究巨噬细胞的具体迁移机制。
消耗EAT巨噬细胞可显著减少相邻心房中的巨噬细胞浸润以及快速心房起搏犬的AF诱导。TRAM-34可显著抑制快速心房起搏犬中巨噬细胞从EAT向相邻心房的迁移以及电重构。与对照HL-1细胞相比，起搏HL-1细胞中CCL2的分泌及迁移的巨噬细胞数量显著增加，而TRAM-34可使其逆转。进一步的体外实验表明，K3.1通过p65/STAT3信号通路调节CCL2分泌。
抑制心肌K3.1可减少快速心房起搏引起的EAT巨噬细胞向相邻心房肌的迁移，从而降低AF易感性。K3.1调节CCL2的机制可能与p65/STAT3信号通路有关。
