Angiotensin-converting enzyme-2 overexpression improves atrial electrical remodeling through TRPM7 signaling pathway.
Angiotensin-converting enzyme-2 overexpression improves atrial electrical remodeling through TRPM7 signaling pathway.
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血管紧张素转换酶2过表达通过TRPM7信号通路改善心房电重构
DOI：
10.18632/oncotarget.20221
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发表时间：
2017-10-03
期刊：
影响因子：
--
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Zhou T;Han Z;Gu J;Chen S;Fan Y;Zhang H;Yin Y;Zhang J;Wang C
心房电重构是心房颤动发生和持续的重要因素。本研究的目的是研究心房血管紧张素转换酶-2过表达对心房电重构的影响，并阐明这些影响的分子机制。将28只雄性和雌性犬随机分为以下4组：假手术组、对照组、腺病毒增强型绿色荧光蛋白（Ad-EGFP）基因组和Ad-ACE 2基因组。Ad-EGFP组和Ad-ACE 2组的所有犬均以450 bpm的频率节律化14天。两周后，所有犬均行开胸和心外膜基因涂绘术。在基因转移后第21天，对所有动物进行电生理和分子研究。与假手术组和Ad-ACE 2组相比，对照组和Ad-EGFP组的AF诱导率和持续时间显著增加。瞬时受体电位melastatin 7（TRPM 7）表达水平在Ad-EGFP组和对照组中显著高于假手术组和Ad-ACE 2组。与对照和非沉默siRNA转染细胞相比，siRNA转染细胞的基础[Mg 2 +]i显著降低。我们的研究结果表明，ACE 2过表达抑制心房电重构，并通过TRPM 7信号通路改善心房功能。
Atrial electrical remodeling is an important factor in the development and persistence of atrial fibrillation. The aim of this study was to examine the effects of atrial angiotensin-converting enzyme-2 overexpression on atrial electrical remodeling and to elucidate the molecular mechanisms underlying these effects. Twenty-eight male and female dogs were randomly divided into the following 4 groups: a sham-operation group, a control group, an adenovirus-enhanced green fluorescent protein (Ad-EGFP) gene group and an Ad-ACE2 gene group. All dogs in the Ad-EGFP and Ad-ACE2 groups were rhythmized at 450 bpm for 14 days. Two weeks later, all the dogs underwent thoracotomy and epicardial gene painting. On day 21 after gene transfer, all the animals were subjected to electrophysiological and molecular studies. AF induction rates and durations were significantly increased in the control and Ad-EGFP groups compared to the sham-operated and Ad-ACE2 groups. Transient receptor potential melastatin 7 (TRPM7) expression levels in the Ad-EGFP and control groups were significantly higher than those in the sham-operated and Ad-ACE2 groups. Basal [Mg2+]i was significantly decreased in siRNA transfected cells compared with control and non-silencing siRNA-transfected cells. Our results suggest that ACE2 overexpression suppresses atrial electrical remodeling and improves atrial function through the TRPM7 signaling pathway.
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