| Author | Giménez, Luis E. D. | |
| Author | Hernández, Ciria C. Q. | |
| Author | Mattos, Elisabete C. | |
| Author | Brandão, Izaira Tincani | |
| Author | Olivieri, Bianca | |
| Author | Campelo, Roberto P. | |
| Author | Araujo-Jorge, Tania C. | |
| Author | Silva, Célio Lopes | |
| Author | Carvalho, Antônio C. Campos de | |
| Author | Kurtenbach, Eleonora | |
| Access date | 2019-12-12T11:56:09Z | |
| Available date | 2019-12-12T11:56:09Z | |
| Document date | 2005 | |
| Citation | GIMÉNEZ, Luis E. D. et al. DNA immunizations with M2 muscarinic and b1 adrenergic receptor coding plasmids impair cardiac function in mice. Journal of Molecular and Cellular Cardiology, v. 38, p. 703-714, 2005. | pt_BR |
| ISSN | 0022-2828 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/37887 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Cardiomiopatia dilatada | pt_BR |
| Subject in Portuguese | Autoimunidade | pt_BR |
| Subject in Portuguese | Autoanticorpo | pt_BR |
| Subject in Portuguese | M2 receptor muscarínico de acetilcolina | pt_BR |
| Subject in Portuguese | Receptor adrenérgico | pt_BR |
| Subject in Portuguese | Imunização de DNA | pt_BR |
| Subject in Portuguese | Ecocardiografia em pequenos animais | pt_BR |
| Title | DNA immunizations with M2 muscarinic and beta1 adrenergic receptor coding plasmids impair cardiac function in mice | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.yjmcc.2004.12.009 | |
| Abstract | Autoimmune mediated myocardial damage is likely to be a pathogenic mechanism for acquired dilated cardiomyopathies. Evidence confirms that autoantibodies that bind to M(2) muscarinic (M(2)AChR) and beta(1) adrenergic receptors (beta(1)AR) are present in idiopathic dilated cardiomyopathy and Chagasic patients' sera. To elucidate the role of these antibodies in cardiac functional impairment, we used a murine model immunized with plasmids encoding the M(2)AChR or beta(1)AR via gene-gun bombardment. Anti-M(2)AChR and beta(1)AR antibodies were detected over the course of 37 weeks. These antibodies were directed to the second extracellular loop (el2) of both receptors and the third intracellular loop (il3) of the M(2)AChR. Peak antibody titers from weeks 2 to 5 against M(2)AChR-el2 and beta(1)AR-el2 as well as elevated titers against M(2)AChR-il3 were detected. Anti-M(2)AChR-il3 and anti-beta(1)AR-el2 antibodies were predominant in IgG1 subclass immunoglobulins, suggesting a T-helper-2 biased lymphocyte response. Heart morphology and function was assessed by echocardiography over the course of 42 weeks. Data showed progressive decrease in left ventricular (LV) wall thickness and LV mass that was mostly evident for beta(1)AR-immunized mice albeit a small change in LV dimensions. Fractional shortening was altered and values of 41%, 37% and 48% were observed at week 42 for the M(2)AChR, beta(1)AR and control groups respectively. In support of autonomic deregulation, a twofold increase in M(2)AChR and a similar decrease in beta(1)AR density were observed in radioligand saturation assays for both experimental groups. Histological analysis revealed myofibril disarray and fibrosis, pointing towards remodeling as a consequence of the long-term presence of anti-receptor antibodies. | pt_BR |
| Affilliation | Universidade Federal de Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Ciências Biomédicas. Departamento de Bioquímica Médica. Rio de Janeiro, RJ, Brasil / Universidade Federal de Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Ecodata Exames Médicos Ltda. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Ciências Biomédicas. Departamento de Bioquímica Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Ecodata Exames Médicos Ltda. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Ciências Biomédicas. Departamento de Bioquímica Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Dilated cardiomyopathy | pt_BR |
| Subject | Autoimmunity | pt_BR |
| Subject | Autoantibody | pt_BR |
| Subject | M2 muscarinic acetylcholine receptor | pt_BR |
| Subject | Adrenergic receptor | pt_BR |
| Subject | DNA immunization | pt_BR |
| Subject | Small animal echocardiography | pt_BR |
| e-ISSN | 1095-8584 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
