Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7381
Title: Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury
Authors: Carvalho, Cristiano Marcelo Espinola
Silvério, Jaline Coutinho
Silva, Andrea Alice da
Pereira, Isabela Resende
Coelho, Janice Mery Chicarino
Britto, Constança Carvalho
Moreira, Otacílio Cruz
Marchevsky, Renato Sergio
Xavier, Sergio Salles
Gazzinelli, Ricardo Tostes
Almeida, Maria da Glória Bonecini de
Vieira, Joseli Lannes
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
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil
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
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 Anatomia Patológica. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. BioManguinhos. Laboratório de Neurovirulência. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Imunologia. Rio de Janeiro, RJ, Brazil
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
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Imunologia. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil
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.
Keywords: Chagas disease
Issue Date: 2012
Publisher: Public Library of Science
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
DOI: 10.1371/journal.pntd.0001644
ISSN: 1873-2550
Copyright: open access
Appears in Collections:Biomanguinhos - Artigos de Periódicos
INI - Artigos de Periódicos
IOC - Artigos de Periódicos
MG - IRR - Artigos de Periódicos



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