Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite <i>Trypanosoma cruzi</i> 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 <i>T....
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Pathogens |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-0817/12/11/1364 |
| _version_ | 1797458127197569024 |
|---|---|
| author | Amanda Fortes Francisco Giovane R. Sousa Mhairi Vaughan Harry Langston Archie Khan Shiromani Jayawardhana Martin C. Taylor Michael D. Lewis John M. Kelly |
| author_facet | Amanda Fortes Francisco Giovane R. Sousa Mhairi Vaughan Harry Langston Archie Khan Shiromani Jayawardhana Martin C. Taylor Michael D. Lewis John M. Kelly |
| author_sort | Amanda Fortes Francisco |
| collection | DOAJ |
| description | Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite <i>Trypanosoma cruzi</i> 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 <i>T. cruzi</i> 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 <i>T. cruzi</i>-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. |
| first_indexed | 2024-03-09T16:32:35Z |
| format | Article |
| id | doaj.art-ad9838ba7cb748409a992a3027604774 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T16:32:35Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-ad9838ba7cb748409a992a30276047742023-11-24T14:59:55ZengMDPI AGPathogens2076-08172023-11-011211136410.3390/pathogens12111364Cardiac Abnormalities in a Predictive Mouse Model of Chagas DiseaseAmanda Fortes Francisco0Giovane R. Sousa1Mhairi Vaughan2Harry Langston3Archie Khan4Shiromani Jayawardhana5Martin C. Taylor6Michael D. Lewis7John M. Kelly8Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKHarvard Medical School, Section on Immunobiology, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USAResearch Department of Haematology, Cancer Institute, Faculty of Medical Sciences, University College London, London WC1E 6DD, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKChronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite <i>Trypanosoma cruzi</i> 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 <i>T. cruzi</i> 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 <i>T. cruzi</i>-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.https://www.mdpi.com/2076-0817/12/11/1364<i>Trypanosoma cruzi</i>electrocardiography (ECG)chronic Chagas cardiomyopathyChagas heart disease |
| spellingShingle | Amanda Fortes Francisco Giovane R. Sousa Mhairi Vaughan Harry Langston Archie Khan Shiromani Jayawardhana Martin C. Taylor Michael D. Lewis John M. Kelly Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease Pathogens <i>Trypanosoma cruzi</i> electrocardiography (ECG) chronic Chagas cardiomyopathy Chagas heart 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 | <i>Trypanosoma cruzi</i> electrocardiography (ECG) chronic Chagas cardiomyopathy Chagas heart disease |
| url | https://www.mdpi.com/2076-0817/12/11/1364 |
| work_keys_str_mv | AT amandafortesfrancisco cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT giovanersousa cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT mhairivaughan cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT harrylangston cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT archiekhan cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT shiromanijayawardhana cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT martinctaylor cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT michaeldlewis cardiacabnormalitiesinapredictivemousemodelofchagasdisease AT johnmkelly cardiacabnormalitiesinapredictivemousemodelofchagasdisease |