PFKM-Driven Lactate Overproduction Promotes Atrial Fibrillation via Triggering Cardiac Fibroblasts Histone Lactylation.

ABSTRACT: Increasing evidence has clarified that atrial fibrillation (AF) is associated with enhanced glycolysis, leading to lactate accumulation. However, whether glycolysis promotes AF remains unknown, as does whether histone lactylation plays a role in its pathogenesis. In the study, spontaneous AF mice are established to monitor AF susceptibility and atrial substrates at different ages (3, 5, 7 months), indicating that enhanced glycolysis acts as a promoter during AF development by inducing atrial fibrosis. The promoting effect of glycolysis on AF and the pivotal enzyme in driving glycolysis are confirmed by treatment with glycolysis inhibitor 2-deoxyglucose (2-DG) and adeno-associated virus-mediated atrial PFKM expression. Furthermore, lactate stimulates primary mouse cardiac fibroblast (CF) ac

SUBMITTER: Fang N 

PROVIDER: S-EPMC12442653 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature