Cardiomyocyte and endothelial cells play distinct roles in the tumor necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice.

Endurance sport is associated with atrial fibrillation (AF) and mouse models show intense exercise training promotes atrial hypertrophy, fibrosis, inflammation, and AF vulnerability, which requires the mechanosensitive inflammatory cytokine tumor necrosis factor (TNF). We demonstrate that Tnf ablation in atrial cardiomyocytes protects fully against atrial changes induced by exercise, whereas endothelial-specific ablation only prevents atrial hypertrophy. Since atrial filling pressures increase markedly during exercise and most clinical conditions linked to AF (hypertension, heart failure, valvular/metabolic diseases), we discuss how atrial stretch may mediate cell autonomous effects of TNF and arrhythmogenic tissue changes in the atria.