Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease.
Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease.
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DOI：
10.3390/pathogens12111364
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发表时间：
2023-11-17
期刊：
影响因子：
--
通讯作者：
Kelly JM
中科院分区：
文献类型：
--
作者：
Francisco AF;Sousa GR;Vaughan M;Langston H;Khan A;Jayawardhana S;Taylor MC;Lewis MD;Kelly JM
慢性恰加斯心肌病 (CCC) 由原生动物寄生虫克氏锥虫感染引起，是流行国家心脏病的常见原因。我们之前发现，慢性感染克氏锥虫 JR 株的 C3H/HeN 小鼠的心脏纤维化差异很大，这反映了人类心脏病的谱系。在这项研究中，我们检查了该宿主：寄生虫组合的功能性心脏异常，以确定其作为 CCC 实验模型的潜力。我们利用心电图 (ECG) 监测克氏锥虫感染的小鼠，并确定心电图标记物是否与心功能异常相关。我们发现C3H/HeN:JR组合经常表现出早期发作的CCC指标，例如窦性心动过缓和右束支传导阻滞，以及急性期PQ、PR、RR、ST和QT间期延长。我们的模型在急性期表现出高水平的心脏炎症和增强的 iNOS 表达，但去神经支配似乎在病理学中没有作用。这些结果证明了 C3H/HeN:JR 宿主:寄生虫组合作为 CCC 模型的潜力，可用于筛选针对心脏重塑的新化合物，并检查抗寄生虫药物预防或减轻 CCC 发生和进展的潜力。
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilised electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST, and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression.
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影响因子：
5.4
作者：
Oliveira, Claudia Di Lorenzo;Nunes, Maria Carmo P.;Ribeiro, Antonio Luiz P.
通讯作者：
Ribeiro, Antonio Luiz P.
影响因子：
--
作者：
Lewis MD;Francisco AF;Taylor MC;Kelly JM
通讯作者：
Kelly JM
影响因子：
2.9
作者：
Haro P;Hevia-Montiel N;Perez-Gonzalez J
通讯作者：
Perez-Gonzalez J
影响因子：
3.4
作者：
Lewis, Michael D.;Francisco, Amanda Fortes;Kelly, John M.
通讯作者：
Kelly, John M.
影响因子：
6.7
作者：
Khan AA;Langston HC;Costa FC;Olmo F;Taylor MC;McCann CJ;Kelly JM;Lewis MD
通讯作者：
Lewis MD