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Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

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 t...

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Autores principales: Francisco, Amanda Fortes, Sousa, Giovane R., Vaughan, Mhairi, Langston, Harry, Khan, Archie, Jayawardhana, Shiromani, Taylor, Martin C., Lewis, Michael D., Kelly, John M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674564/
https://www.ncbi.nlm.nih.gov/pubmed/38003828
http://dx.doi.org/10.3390/pathogens12111364
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author Francisco, Amanda Fortes
Sousa, Giovane R.
Vaughan, Mhairi
Langston, Harry
Khan, Archie
Jayawardhana, Shiromani
Taylor, Martin C.
Lewis, Michael D.
Kelly, John M.
author_facet Francisco, Amanda Fortes
Sousa, Giovane R.
Vaughan, Mhairi
Langston, Harry
Khan, Archie
Jayawardhana, Shiromani
Taylor, Martin C.
Lewis, Michael D.
Kelly, John M.
author_sort Francisco, Amanda Fortes
collection PubMed
description 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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spelling pubmed-106745642023-11-17 Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease Francisco, Amanda Fortes Sousa, Giovane R. Vaughan, Mhairi Langston, Harry Khan, Archie Jayawardhana, Shiromani Taylor, Martin C. Lewis, Michael D. Kelly, John M. Pathogens Article 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. MDPI 2023-11-17 /pmc/articles/PMC10674564/ /pubmed/38003828 http://dx.doi.org/10.3390/pathogens12111364 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Francisco, Amanda Fortes
Sousa, Giovane R.
Vaughan, Mhairi
Langston, Harry
Khan, Archie
Jayawardhana, Shiromani
Taylor, Martin C.
Lewis, Michael D.
Kelly, John M.
Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title_full Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title_fullStr Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title_full_unstemmed Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title_short Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
title_sort cardiac abnormalities in a predictive mouse model of chagas disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674564/
https://www.ncbi.nlm.nih.gov/pubmed/38003828
http://dx.doi.org/10.3390/pathogens12111364
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