Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia-Induced Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Recently, it was reported that mast cells (MCs) could underlie the mechanisms of several cardiovascular diseases. However, the role of MCs in diabetes-induced atrial fibrillation (AF) has not been notably investigated. We tested the hypothesis that MC deficiency attenuates hyperglycemia-induced AF in mice. METHODS AND RESULTS: Mast cell-deficient W/W(v)  mice, and congenic +/+ littermates (WT) were divided into either the vehicle (VEH)-injection group or the streptozotocin (STZ)-injection group (MCKO-VEH, MCKO-STZ, WT-VEH, and WT-STZ groups). On day 28 of our studies, we observed that (1) STZ-induced hyperglycemia increased MC infiltration in the left atrium (LA) in WT mice (P < 0.01), (2) atrium isolated from the WT-STZ group showed inhomogeneous interstitial fibrosis, abundant infiltration of macrophages, and enhanced apoptosis compared to the WT-VEH group (P < 0.01, P < 0.01, P < 0.05, respectively). However, the changes observed in the WT-STZ group were significantly attenuated in the MCKO-STZ mice. In addition, we observed that (3) messenger RNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, transforming growth factor-β, and collagen-1 in the LA were increased in the WT-STZ group, but not in the MCKO-STZ group, (4) STZ-induced hyperglycemia increased AF induction and prolonged interatrial conduction time in the WT mice, which were not observed in the MCKO mice, and that (5) hyperglycemia-enhanced atrial production of reactive oxygen species (ROS) was equally observed in the WT and MCKO mice. CONCLUSIONS: Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.