DYNLT1 Deficiency Induces Atrial Fibrillation: Insights into Cardiac Remodeling and Molecular Mechanisms

Atrial fibrillation (AF) is a prevalent arrhythmia characterized by high morbidity and mortality, yet its molecular underpinnings remain poorly understood. This study investigates the role of DYNLT1 in AF by generating a DYNLT1-knockout (KO) mouse model via CRISPR/Cas9 technology. Molecular analyses revealed significant disruptions in key pathways, including reduced expression of gap junction proteins connexin 40 and 43, increased cardiomyocyte apoptosis as indicated by TUNEL staining, and heightened inflammatory responses characterized by elevated IL-6, CRP, and TNF-α levels. These molecular changes were accompanied by structural remodeling, including atrial enlargement and fibrosis, as demonstrated by histological analyses and echocardiography. Electrocardiographic recordings showed prolonged PR intervals, irregular RR intervals, and reduced P-wave amplitude, confirming electrophysiological remodeling. Pharmacological testing highlighted the model’s sensitivity to antiarrhythmic drugs such as amiodarone and propafenone, which effectively restored sinus rhythm. These findings establish DYNLT1 as a key regulator in AF pathogenesis and underscore the KO mouse model as a valuable tool for exploring the molecular and cellular mechanisms of AF and for screening potential therapeutic agents.