A novel murine model of atrial fibrillation by diphtheria toxin-induced injury.
A novel murine model of atrial fibrillation by diphtheria toxin-induced injury.
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DOI：
10.3389/fphys.2022.977735
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发表时间：
2022
影响因子：
4
通讯作者：
Nakano, Atsushi
中科院分区：
文献类型：
--
作者：
Trieu, Theresa;Mach, Philbert;Bunn, Kaitlyn;Huang, Vincent;Huang, Jamie;Chow, Christine;Nakano, Haruko;Fajardo, Viviana M.;Touma, Marlin;Ren, Shuxun;Wang, Yibin;Nakano, Atsushi
心房颤动（AF）的治疗仍然是一个重大的临床挑战。全基因组关联研究 (GWAS) 开始识别 AF 易感基因（Gudbjartsson 等人，Nature, 2007, 448, 353–357；Choi 等人，Circ. Res., 2020, 126, 200–209；van Ouwerkerk 等人，Circ. Res., 2022, 127， 229-243），包括物理、化学和生物环境在内的非遗传风险因素仍然是房颤发生的主要因素。然而，关于非遗传危险因素如何促进房颤的发病机制，人们知之甚少（Weiss et al., Heart Rhythm, 2016, 13, 1868–1877；Chakraborty et al., Heart Rhythm, 2020, 17, 1,398–1,404；Nattel et al., Circ. Res., 2020, 127、51-72）。这在一定程度上是由于缺乏由非遗传因素诱导的稳健可靠的动物模型。目前使用快速起搏协议的模型无法在啮齿动物模型中产生稳定的 AF 表型，通常需要额外的基因修饰，从而引入潜在的偏差来源（Schüttler 等人，Circ. Res.，2020, 127, 91–110）。在这里，我们报告了一种新型的 AF 小鼠模型，该模型利用白喉毒素 (DT) 介导的细胞损伤系统的诱导性和组织特异性激活。通过人 HB-EGF 在心房肌细胞中的组织特异性和诱导性表达，我们开发了一种可靠、稳健且可扩展的 AF 小鼠模型，该模型由非遗传诱导剂触发，无需 AF 易感基因突变。
The treatment of atrial fibrillation (AF) continues to be a significant clinical challenge. While genome-wide association studies (GWAS) are beginning to identify AF susceptibility genes (Gudbjartsson et al., Nature, 2007, 448, 353–357; Choi et al., Circ. Res., 2020, 126, 200–209; van Ouwerkerk et al., Circ. Res., 2022, 127, 229–243), non-genetic risk factors including physical, chemical, and biological environments remain the major contributors to the development of AF. However, little is known regarding how non-genetic risk factors promote the pathogenesis of AF (Weiss et al., Heart Rhythm, 2016, 13, 1868–1877; Chakraborty et al., Heart Rhythm, 2020, 17, 1,398–1,404; Nattel et al., Circ. Res., 2020, 127, 51–72). This is, in part, due to the lack of a robust and reliable animal model induced by non-genetic factors. The currently available models using rapid pacing protocols fail to generate a stable AF phenotype in rodent models, often requiring additional genetic modifications that introduce potential sources of bias (Schüttler et al., Circ. Res., 2020, 127, 91–110). Here, we report a novel murine model of AF using an inducible and tissue-specific activation of diphtheria toxin (DT)-mediated cellular injury system. By the tissue-specific and inducible expression of human HB-EGF in atrial myocytes, we developed a reliable, robust and scalable murine model of AF that is triggered by a non-genetic inducer without the need for AF susceptibility gene mutations.
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影响因子：
37.8
作者：
January CT;Wann LS;Alpert JS;Calkins H;Cigarroa JE;Cleveland JC Jr;Conti JB;Ellinor PT;Ezekowitz MD;Field ME;Murray KT;Sacco RL;Stevenson WG;Tchou PJ;Tracy CM;Yancy CW;ACC/AHA Task Force Members
通讯作者：
ACC/AHA Task Force Members
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A
影响因子：
20.1
作者：
Verheule, S;Sato, T;Olgin, JE
通讯作者：
Olgin, JE
影响因子：
20.1
作者：
Schuettler, Dominik;Bapat, Aneesh;Hucker, William J.
通讯作者：
Hucker, William J.
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影响因子：
5.4
作者：
Davies L;Jin J;Shen W;Tsui H;Shi Y;Wang Y;Zhang Y;Hao G;Wu J;Chen S;Fraser JA;Dong N;Christoffels V;Ravens U;Huang CL;Zhang H;Cartwright EJ;Wang X;Lei M
通讯作者：
Lei M