Author | Carvalho, Cristiano Marcelo Espinola | |
Author | Silvério, Jaline Coutinho | |
Author | Silva, Andrea Alice da | |
Author | Pereira, Isabela Resende | |
Author | Coelho, Janice Mery Chicarino | |
Author | Britto, Constança Carvalho | |
Author | Moreira, Otacílio Cruz | |
Author | Marchevsky, Renato Sergio | |
Author | Xavier, Sergio Salles | |
Author | Gazzinelli, Ricardo Tostes | |
Author | Almeida, Maria da Glória Bonecini de | |
Author | Vieira, Joseli Lannes | |
Access date | 2014-03-07T13:25:29Z | |
Available date | 2014-03-07T13:25:29Z | |
Document date | 2012 | |
Citation | CARVALHO, Cristiano Marcelo Espinola et al. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury. Plos Neglected Tropical Disease. 2012, vol.6, pp. e1644 | pt_BR |
ISSN | 1873-2550 | |
URI | https://www.arca.fiocruz.br/handle/icict/7381 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | |
Title | Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury | pt_BR |
Type | Article | |
DOI | 10.1371/journal.pntd.0001644 | |
Abstract | Background: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2−/−) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection.
Methodology: Rhesus monkeys and C57BL/6 and Nos2−/− mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue.
Results: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2−/− mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue.
Conclusion: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC severity, mainly disturbing of the molecular pathway involved in electrical synchrony. These findings open a new avenue for therapeutic tools in Chagas' heart disease. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil/ Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Imunologia. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil/ Universidade Federal Fluminense. Departamento de Patologia. Niterói, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Anatomia Patológica. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. BioManguinhos. Laboratório de Neurovirulência. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Imunologia. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunoparasitologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Imunologia e Bioquímica. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Imunologia. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil | pt_BR |
Subject | Chagas disease | pt_BR |