Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia-Induced Atrial Fibrillation
Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia-Induced Atrial Fibrillation
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DOI：
10.1111/jce.12995
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发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Takahashi, Naohiko
中科院分区：
文献类型：
--
作者：
Uemura, Kenshi;Kondo, Hidekazu;Takahashi, Naohiko
肥大细胞在高血糖诱导的心房重构中的作用研究背景与目的近年来，肥大细胞（Mast cell，MC）被认为是多种心血管疾病发生机制的基础。然而，MC在糖尿病诱发的心房颤动（AF）中的作用尚未得到显著研究。我们测试的假设，MC缺陷减弱高血糖诱导的AF在mice.Methods和Results肥大细胞缺陷W/W（v）小鼠，和同源+/+同窝（WT）被分为无论是车辆（VEH）注射组或链脲佐菌素（STZ）注射组（MCKO-VEH，MCKO-STZ，WT-VEH，WT-STZ组）。在我们研究的第28天，我们观察到（1）STZ诱导的高血糖增加了WT小鼠左心房（LA）中的MC浸润（2）与WT-VEH组相比，WT-STZ组大鼠心房组织间质纤维化程度不均匀，巨噬细胞大量浸润，细胞凋亡增加（P < 0.01、P < 0.01、P < 0.05）。然而，在WT-STZ组中观察到的变化在MCKO-STZ小鼠中显著减弱。此外，我们观察到（3）在WT-STZ组中，LA中肿瘤坏死因子-、单核细胞趋化蛋白-1、白细胞介素-1、转化生长因子-和胶原-1的信使RNA水平增加，但在MCKO-STZ组中没有增加;（4）STZ诱导的高血糖增加了WT小鼠的AF诱导和房间传导时间延长，而在MCKO小鼠中没有观察到，（5）WT和MCKO小鼠心房活性氧（ROS）的产生均明显增加。结论MCs通过增强炎症和纤维化参与了高血糖诱发的AF的发病机制。
Roles of Mast Cells in Hyperglycemia-Induced Atrial RemodelingBackground and ObjectivesRecently, 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 ResultsMast 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-, monocyte chemoattractant protein-1, interleukin-1, transforming growth factor-, 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.ConclusionsOur results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.