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Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
Amanda Fortes Francisco1, Giovane R Sousa2, Mhairi Vaughan3
1Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Insights
A new mouse model using the Trypanosoma cruzi parasite effectively mimics human Chronic Chagas cardiomyopathy (CCC). This model shows early indicators of heart disease, aiding research into new treatments for this prevalent condition.
Area of Science:
- Cardiology
- Infectious Diseases
- Parasitology
Background:
- Chronic Chagas cardiomyopathy (CCC) is a significant cause of heart disease in endemic regions, stemming from Trypanosoma cruzi infection.
- Previous studies noted variable cardiac fibrosis in C3H/HeN mice infected with T. cruzi JR strain, similar to human CCC spectrum.
- The C3H/HeN:JR host:parasite combination was investigated for its potential as an experimental model for CCC.
Purpose of the Study:
- To evaluate the C3H/HeN:JR host:parasite combination as a model for Chronic Chagas cardiomyopathy (CCC).
- To identify and correlate electrocardiographic (ECG) markers with cardiac functional abnormalities in T. cruzi-infected mice.
Main Methods:
- Utilized electrocardiography (ECG) to monitor T. cruzi-infected C3H/HeN mice.
- Assessed cardiac inflammation and inducible nitric oxide synthase (iNOS) expression.
- Investigated the role of denervation in the observed pathology.
Main Results:
- The C3H/HeN:JR model frequently exhibited early CCC indicators, including sinus bradycardia and right bundle branch block.
- Prolonged PQ, PR, RR, ST, and QT intervals were observed in the acute stage.
- High cardiac inflammation and enhanced iNOS expression were present in the acute stage; denervation was not implicated.
Conclusions:
- The C3H/HeN:JR host:parasite combination serves as a viable experimental model for CCC.
- This model can be used for screening therapeutic compounds targeting cardiac remodeling.
- It also facilitates examination of antiparasitic drugs for preventing or mitigating CCC development and progression.
Abstract:
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.
