Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction.

• Tác giả: Lucas Arantes Berg, Julia Camps, Carla de Villiers, Neil Herring, Hector Martinez-Navarro, Leto Luana Riebel, Paul R Riley, Blanca Rodriguez, Claudio Cortes Rodriguez, Tatjana Sauka-Spengler, Judy R Sayers, Sarah Sigal, Xin Sun, Michael Weinberger
• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.1237 Diseases of cardiovascular system
• Thông tin xuất bản: England : Nature cardiovascular research , 2025
• Bộ sưu tập: NCBI
• ID: 60197

Tóm tắt

Arrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological remodeling at non-regenerative stages. Tissue-cleared whole-organ imaging identified disorganized bundling of conduction fibers after MI and global His-Purkinje disruption. Single-cell RNA sequencing (scRNA-seq) revealed specific molecular changes to regenerate the conduction network versus aberrant electrical alterations during fibrotic repair. This manifested functionally as a transition from normal rhythm to pathological conduction delay beyond the regenerative window. Modeling in the infarcted human heart implicated the non-regenerative phenotype as causative for heart block, as observed in patients. These findings elucidate the mechanisms underpinning conduction system regeneration and reveal how MI-induced damage elicits clinical arrhythmogenesis.