Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease
Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart...
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Published in | Memórias do Instituto Oswaldo Cruz Vol. 109; no. 3; pp. 289 - 298 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Brazil
Fundação Oswaldo Cruz, Fiocruz
01.06.2014
Instituto Oswaldo Cruz, Ministério da Saúde Fundação Oswaldo Cruz (FIOCRUZ) |
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Abstract | Heart tissue inflammation, progressive fibrosis and
electrocardiographic alterations occur in approximately 30% of patients
infected by Trypanosoma cruzi, 10-30 years after infection. Further,
plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are
associated with the degree of heart dysfunction in chronic chagasic
cardiomyopathy (CCC). Thus, our aim was to establish experimental
models that mimic a range of parasitological, pathological and cardiac
alterations described in patients with chronic Chagas' heart
disease and evaluate whether heart disease severity was associated with
increased TNF and NO levels in the serum. Our results show that C3H/He
mice chronically infected with the Colombian T. cruzi strain have more
severe cardiac parasitism and inflammation than C57BL/6 mice. In
addition, connexin 43 disorganisation and fibronectin deposition in the
heart tissue, increased levels of creatine kinase cardiac MB isoenzyme
activity in the serum and more severe electrical abnormalities were
observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice.
Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe
and mild models of CCC, respectively. Moreover, the CCC severity
paralleled the TNF and NO levels in the serum. Therefore, these models
are appropriate for studying the pathophysiology and biomarkers of CCC
progression, as well as for testing therapeutic agents for patients
with Chagas' heart disease. |
---|---|
AbstractList | Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease. Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi , 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi- infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi -infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease. Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas' heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas' heart disease. |
Author | Vilar-Pereira, Glaucia Pereira, Isabela Resende da Silva, Andrea Alice Lannes-Vieira, Joseli |
AuthorAffiliation | 1 Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil 2 Departamento de Patologia, Universidade Federal Fluminense, Niterói, RJ, Brasil |
AuthorAffiliation_xml | – name: 1 Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil – name: 2 Departamento de Patologia, Universidade Federal Fluminense, Niterói, RJ, Brasil – name: Fundação Oswaldo Cruz – name: Universidade Federal Fluminense |
Author_xml | – sequence: 1 fullname: Pereira, Isabela Resende – sequence: 2 fullname: Vilar-Pereira, Glaucia – sequence: 3 fullname: da Silva, Andrea Alice – sequence: 4 fullname: Lannes-Vieira, Joseli |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24937048$$D View this record in MEDLINE/PubMed |
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Keywords | Chagas disease nitric oxide tumour necrosis factor experimental model cardiomyopathy |
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Snippet | Heart tissue inflammation, progressive fibrosis and
electrocardiographic alterations occur in approximately 30% of patients
infected by Trypanosoma cruzi,... Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi,... Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi ,... |
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SubjectTerms | Animals Biomarkers - blood cardiomyopathy Chagas Cardiomyopathy - blood Chagas Cardiomyopathy - pathology Chagas Cardiomyopathy - physiopathology Chagas disease Chronic Disease Disease Models, Animal experimental model Female Mice Mice, Inbred C3H Mice, Inbred C57BL nitric oxide Nitric Oxide - blood PARASITOLOGY Severity of Illness Index TROPICAL MEDICINE Tumor Necrosis Factors - blood tumour necrosis factor |
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Title | Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease |
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