REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiac Rhythmology
This article is part of the Research TopicPrecision Strategies for Atrial Fibrillation: Diagnosis, Risk, and Treatment InnovationsView all 13 articles
Inflammatory and Fibrotic Signaling Pathways Mediated by Cardiac Macrophages in Atrial Fibrillation
Provisionally accepted
- 1Nanchang University Jiangxi Medical College, Nanchang, China
- 2Jiangxi Provincial People's Hospital, Nanchang, China
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Atrial fibrillation (AF) is traditionally characterized as an electrophysiological disorder; however, growing evidence underscores its intimate connection with immune dysregulation, particularly inflammation-driven structural remodeling. This review aims to comprehensively elucidate the role of cardiac macrophages in AF pathogenesis, focusing on their involvement in inflammatory and fibrotic signaling, electrical remodeling, and intercellular interactions. By systematically reviewed previous studies, this review summarises how macrophages act as central modulators of AF through phenotype-specific mechanisms. M1-polarized macrophages contribute to electrical instability by releasing pro-inflammatory cytokines that affect ion channel expression and action potential duration. In contrast, M2 macrophages promote fibroblast activation and collagen deposition transforming growth factor-beta 1(TGF-β1), interleukin-10 (IL-10), and Tumor Necrosis Factor Superfamily Member 14 (LIGHT) signaling, leading to atrial fibrosis. Evidence from human samples, animal experiments, and transcriptomic data converge on macrophage density, polarization state, and cytokine signatures as key correlates of AF severity and recurrence. Targeting their activation states and signaling pathways represents a promising avenue for mechanism-guided AF therapy. Therefore, this review provides a consolidated framework for future translational strategies aiming to interrupt the immune-mediated remodeling cascade in AF.
Keywords: Atrial Fibrillation, Cardiac macrophages, ATRIAL REMODELING, Inflammation, Fibrosis
Received: 26 Aug 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Ren, Lai and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hengli Lai
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