Karakasis Paschalis, Theofilis Panagiotis, Milaras Nikias, Vlachakis Panayotis K, Patoulias Dimitrios, Karamitsos Theodoros, Antoniadis Antonios P, Fragakis Nikolaos
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece.
First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Int J Mol Sci. 2025 May 29;26(11):5253. doi: 10.3390/ijms26115253.
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation-comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs-has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways-ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing-are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance.
心房颤动（AF）是最常见的持续性心律失常，与显著的发病率、死亡率及医疗负担相关。尽管治疗取得了进展，但复发率仍然很高，尤其是在持续性房颤中，这凸显了深入了解发病机制的必要性。表观遗传调控——包括DNA甲基化、组蛋白修饰、染色质重塑、RNA甲基化和非编码RNA——已成为房颤潜在的结构、电和炎症重塑的关键促成因素。这些机制在遗传易感性和环境暴露的界面上发挥作用，为理解疾病进展提供了一个动态框架。衰老、肥胖、糖尿病、高血压、缺氧和酒精等全身性应激源已被证明可诱导心房组织中的表观遗传重编程，进一步促进心房心肌病和心律失常的发生。此外，正在研究循环表观遗传标记物，特别是微小RNA在房颤诊断、风险分层和治疗监测中的潜力。针对表观遗传途径的治疗策略——从组蛋白去乙酰化酶抑制剂和基于微小RNA的疗法到CRISPR/dCas9介导的表观基因组编辑——正在研究中。此外，钠-葡萄糖协同转运蛋白2抑制剂可能间接影响与心房重塑相关的表观遗传程序和微小RNA表达。尽管前景广阔，但这些方法在安全性、递送特异性和长期疗效方面需要进一步验证。高分辨率表观基因组图谱和综合多组学方法可能会增强对房颤异质性的理解，并实现个性化治疗策略。本综述对房颤中的表观遗传机制进行了综合评估，并概述了它们新出现的诊断和治疗意义。
