Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.
Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.
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亨廷顿病 BACHD 小鼠模型中进行性心律失常和心电图异常。
DOI：
10.1093/hmg/ddz295
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发表时间：
2020
影响因子：
3.5
通讯作者：
Huke,Sabine
中科院分区：
文献类型：
--
作者：
Zhu,Yujie;Shamblin,Isaac;Rodriguez,Efrain;Salzer,GraceE;Araysi,Lita;Margolies,KatherineA;Halade,GaneshV;Litovsky,SilvioH;Pogwizd,Steven;Gray,Michelle;Huke,Sabine
亨廷顿氏病（HD）是一种主要遗传的神经退行性疾病。越来越多的证据表明，HD患者传导异常和窦房结功能受损的患病率增加，这可能导致心律失常的风险增加。我们使用表达细菌人工染色体亨廷顿氏病小鼠的突变亨廷顿蛋白（mHTT）来确定它们是否表现出涉及心脏传导的心电图（ECG）异常，这种异常已知会增加人类突然心律失常死亡的风险。获得体表心电图，分析心律失常易感性；我们观察到QRS持续时间延长，室性早搏和PACs增加。组织学和结构的异常改变可导致心脏传导系统功能障碍。最后，我们观察到桥粒体蛋白，plakophilin-2和桥粒蛋白-2的减少，这些蛋白被报道会导致心律失常和传导减少。我们的研究表明mHTT可引起进行性心脏传导系统病理，增加HD患者心律失常和心源性猝死的易感性。
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington’s disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans. We obtained surface ECGs and analyzed arrhythmia susceptibility; we observed prolonged QRS duration, increases in PVCs as well as PACs. Abnormal histological and structural changes that could lead to cardiac conduction system dysfunction were seen. Finally, we observed decreases in desmosomal proteins, plakophilin-2 and desmoglein-2, which have been reported to cause cardiac arrhythmias and reduced conduction. Our study indicates that mHTT could cause progressive cardiac conduction system pathology that could increase the susceptibility to arrhythmias and sudden cardiac death in HD patients.