Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease.
Amanda Fortes FranciscoGiovane R SousaMhairi VaughanHarry LangstonArchie KhanShiromani JayawardhanaMartin Craig TaylorMichael D LewisJohn M KellyPublished in: Pathogens (Basel, Switzerland) (2023)
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.
Keyphrases
- trypanosoma cruzi
- early onset
- left ventricular
- drug induced
- mouse model
- liver failure
- poor prognosis
- oxidative stress
- late onset
- heart failure
- plasmodium falciparum
- respiratory failure
- heart rate variability
- toxoplasma gondii
- high fat diet induced
- blood pressure
- metabolic syndrome
- adipose tissue
- long non coding rna
- atrial fibrillation
- nitric oxide
- binding protein
- climate change