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



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.



Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Kenshi
K
Uemura
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Hidekazu
H
Kondo
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Yumi
Y
Ishii
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Mami
M
Kobukata
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Miho
M
Haraguchi
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Takaaki
T
Imamura
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Toyokazu
T
Otsubo
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Yuki
Y
Ikebe-Ebata
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Ichitaro
I
Abe
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Reika
R
Ayabe
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Shotaro
S
Saito
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Oita University Faculty of Medicine, Oita, Japan.
Kohei
K
Aoki
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Yasuko
Y
Nagano-Torigoe
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Hidefumi
H
Akioka
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Tetsuji
T
Shinohara
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Yasushi
Y
Teshima
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Oita University Faculty of Medicine, Oita, Japan.
Takayuki
T
Masaki
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Kunio
K
Yufu
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Mikiko
M
Nakagawa
Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
Naohiko
N
Takahashi
D000818:Animals; D017209:Apoptosis; D001281:Atrial Fibrillation / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D005355:Fibrosis; D018836:Inflammation Mediators / Q000097:blood; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D024042:Collagen Type I; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
atrial fibrillation; hyperglycemia; inflammatory fibrosis; mast cell; reactive oxygen species