Activation of AMP-Activated Protein Kinases Prevents Atrial Fibrillation.

Abstract

Atrial fibrillation (AF) is common, yet there is no preventive therapy for AF. We tested the efficacy of AMP-activated protein kinase (AMPK) activators, metformin, and aspirin, in primary prevention of AF in cardiac-specific liver kinase B1 (LKB1) knockout (KO) mouse model of AF. Incidence of spontaneous AF was significantly reduced in treated KO mice with metformin (10mg/kg/day) (8.3% in male and 10.3% in female) and aspirin (20mg/kg/day) (29.4% in male and 21.4% in female) compared with untreated littermates (81% in male and 67% in female) at 8weeks (p < 0.05). Prevention of AF was associated with activation of AMPK in treated mice and thereby improvement of mitochondrial function, gap junction proteins (connexin 40/43), and intra- and inter-cellular ultrastructure in atrial myocardium. Fibrosis was significantly less in treated mice atria. Pharmacological activation of AMPK is an effective upstream therapy for the primary prevention of AF in susceptible heart. Graphical abstract.