Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.
Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.
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心房过度表达血管紧张素转换酶 2 可改善犬快速心房起搏引起的结构和电重塑。
DOI：
10.1007/s00395-015-0499-0
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发表时间：
2015
影响因子：
9.5
通讯作者：
Yin Y
中科院分区：
文献类型：
--
作者：
Fan J;Zou L;Cui K;Woo K;Du H;Chen S;Ling Z;Zhang Q;Zhang B;Lan X;Su L;Zrenner B;Yin Y
本研究的目的是在犬心房起搏模型上研究心房血管紧张素转换酶2（ACE 2）基因转染是否能逆转心房重构及其机制。将28只杂种犬随机分为4组：假手术组、AF对照组、腺病毒增强型绿色荧光蛋白（Ad-EGFP）基因治疗组和腺病毒介导的血管紧张素转换酶2（Ad-ACE 2）基因治疗组，每组7只。除假手术组外，其余犬均以450次/min的速度快速心房起搏2周诱发房颤。Ad-EGFP组和Ad-ACE 2组行心外膜基因涂敷。转基因3周后，除Sham组外，所有动物均接受快速心房起搏3周，然后进行有创电生理、组织学和分子生物学研究。与Ad-EGFP和AF对照组相比，Ad-ACE 2组ACE 2和Ang-（1-7）表达增加，Ang-II表达减少。ACE 2过表达减弱了快速心房起搏诱导的活化细胞外信号调节激酶和丝裂原活化蛋白激酶（MAPK）水平的升高，以及MAPK磷酸酶1（MKP-1）水平的降低，导致心房纤维化胶原蛋白标志物和转化生长因子-β1的减弱。ACE 2过表达还可调节心脏起搏诱导的连接蛋白40上调、连接蛋白43和Kv4.2下调，并显著缩短房颤的发生和持续时间。ACE 2过表达可使肾素-血管紧张素系统平衡向保护轴方向移动，减轻与MKP-1上调和MAPK活性降低相关的心脏纤维化重塑，调节快速起搏诱导的离子通道和连接蛋白重塑，并随后减少AF的诱导和持续时间。本文的在线版本（doi：10.1007/s 00395 -015-0499-0）包含补充材料，可供授权用户使用。
The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1–7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin–angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF. The online version of this article (doi:10.1007/s00395-015-0499-0) contains supplementary material, which is available to authorized users.
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发表时间：
2008-02-01
影响因子：
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