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 reviewing 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- β 1), 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.
Ren et al. (2026) studied this question. M1-polarized macrophages contribute to electrical instability in atrial fibrillation, while M2 macrophages promote fibrosis, correlating with AF severity and recurrence.