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Levels of circulating anti-muscarinic and anti-adrenergic antibodies and their effect on cardiac arrhythmias and dysautonomia in murine models of Chagas disease

Published online by Cambridge University Press:  05 August 2014

ANISSA DALIRY
Affiliation:
Laboratório de Investigação Cardiovascular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil
ISABELA RESENDE PEREIRA
Affiliation:
Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
PEDRO PAULO PEREIRA-JUNIOR
Affiliation:
Laboratório de Eletrofisiologia Cardíaca, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil
ISALIRA PEROBA RAMOS
Affiliation:
Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
GLAUCIA VILAR-PEREIRA
Affiliation:
Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
RAQUEL RANGEL SILVARES
Affiliation:
Laboratório de Investigação Cardiovascular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
JOSELI LANNES-VIEIRA
Affiliation:
Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
ANTÔNIO CARLOS CAMPOS DE CARVALHO*
Affiliation:
Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil
*
* Corresponding author: Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Av. Carlos Chagas Filho, 373, Bloco G, sala G2-045, Cidade Universitária, Rio de Janeiro, RJ, CEP 21941-902, Brazil. E-mail: [email protected]

Summary

Antibodies (Ab) recognizing G-protein coupled receptors, such as β 1 and β 2 adrenergic (anti-β 1-AR and anti-β 2-AR, respectively) and muscarinic cholinergic receptors (anti-M2-CR) may contribute to cardiac damage, however their role in chronic chagasic cardiomyopathy is still controversial. We describe that Trypanosoma cruzi-infected C3H/He mice show increased P and QRS wave duration, and PR and QTc intervals, while the most significant ECG alterations in C57BL/6 are prolonged P wave and PR interval. Echocardiogram analyses show right ventricle dilation in infected animals of both mouse lineages. Analyses of heart rate variability (HRV) in chronically infected C3H/He mice show no alteration of the evaluated parameters, while C57BL/6 infected mice display significantly lower values of HRV components, suggesting autonomic dysfunction. The time-course analysis of anti-β 1-AR, anti-β 2-AR and anti-M2-CR Ab titres in C3H/He infected mice indicate that anti-β 1-AR Ab are detected only in the chronic phase, while anti-β 2-AR and anti-M2-CR are observed in the acute phase, diminish at 60 dpi and increase again in the chronic phase. Chronically infected C57BL/6 mice presented a significant increase in only anti-M2-CR Ab titres. Furthermore, anti-β 1-AR, anti-β 2-AR and anti-M2-CR, exhibit significantly higher prevalence in chronically T. cruzi-infected C3H/He mice when compared with C57BL/6. These observations suggest that T. cruzi infection leads to host-specific cardiac electric alterations.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2014 

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References

REFERENCES

Bern, C. and Montgomery, S. P. (2009). An estimate of the burden of Chagas disease in the United States. Clinical Infectious Diseases 49, e52e54.Google Scholar
Bilate, A. M. and Cunha-Neto, E. (2008). Chagas disease cardiomyopathy: current concepts of an old disease. Revista do Instituto de Medicina Tropical de Sao Paulo 50, 6774.Google Scholar
Borda, E. S. and Sterin-Borda, L. (1996). Antiadrenergic and muscarinic receptor antibodies in Chagas’ cardiomyopathy. International Journal of Cardiology 54, 149156.Google Scholar
Brener, Z. and Gazzinelli, R. T. (1997). Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas’ disease. International Archives of Allergy and Immunology 114, 103110.CrossRefGoogle ScholarPubMed
Cossio, P. M., Diez, C., Szarfman, A., Kreutzer, E., Candiolo, B. and Arana, R. M. (1974). Chagasic cardiopathy. Demonstration of a serum gamma globulin factor which reacts with endocardium and vascular structures. Circulation 49, 1321.Google Scholar
Cunha-Neto, E., Bilate, A. M., Hyland, K. V., Fonseca, S. G., Kalil, J. and Engman, D. M. (2006). Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39, 4154.CrossRefGoogle ScholarPubMed
Daliry, A., Caldas, I. S., de Figueiredo Diniz, L., Torres, R. M., Talvani, A., Bahia, M. T. and Campos de Carvalho, A. C. (2014). Anti-adrenergic and muscarinic receptor autoantibodies in a canine model of Chagas disease and their modulation by benznidazole. International Journal of Cardiology 170, e66e67.Google Scholar
Dandel, M., Wallukat, G., Potapov, E. and Hetzer, R. (2012). Role of beta(1)-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy. Immunobiology 217, 511520.Google Scholar
de Oliveira, S. F., Pedrosa, R. C., Nascimento, J. H., Campos de Carvalho, A. C. and Masuda, M. O. (1997). Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts. Circulation 96, 20312037.Google Scholar
dos Santos, P. V., Roffe, E., Santiago, H. C., Torres, R. A., Marino, A. P., Paiva, C. N., Silva, A. A., Gazzinelli, R. T. and Lannes-Vieira, J. (2001). Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules. Microbes and Infection 3, 971984.Google Scholar
Eickhoff, C. S., Lawrence, C. T., Sagartz, J. E., Bryant, L. A., Labovitz, A. J., Gala, S. S. and Hoft, D. F. (2010). ECG detection of murine chagasic cardiomyopathy. Journal of Parasitology 96, 758764.CrossRefGoogle ScholarPubMed
Elies, R., Ferrari, I., Wallukat, G., Lebesgue, D., Chiale, P., Elizari, M., Rosenbaum, M., Hoebeke, J. and Levin, M. J. (1996). Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas’ disease. Journal of Immunology 157, 42034211.Google Scholar
Escobar, A. L., Fernandez-Gomez, R., Peter, J. C., Mobini, R., Hoebeke, J. and Mijares, A. (2006). IgGs and Mabs against the beta2-adrenoreceptor block A-V conduction in mouse hearts: a possible role in the pathogenesis of ventricular arrhythmias. Journal of Molecular and Cellular Cardiology 40, 829837.CrossRefGoogle Scholar
Feldman, D. S., Carnes, C. A., Abraham, W. T. and Bristow, M. R. (2005). Mechanisms of disease: beta-adrenergic receptors – alterations in signal transduction and pharmacogenomics in heart failure. Nature Clinical Practice Cardiovascular Medicine 2, 475483.Google Scholar
Gascon, J., Albajar, P., Canas, E., Flores, M., Gomez i Prat, J., Herrera, R. N., Lafuente, C. A., Luciardi, H. L., Moncayo, A., Molina, L., Munoz, J., Puente, S., Sanz, G., Trevino, B. and Sergio-Salles, X. (2007). [Diagnosis, management and treatment of chronic Chagas’ heart disease in areas where Trypanosoma cruzi infection is not endemic.] Revista espanola de cardiologia 60, 285293.Google Scholar
Goin, J. C., Borda, E., Leiros, C. P., Storino, R. and Sterin-Borda, L. (1994). Identification of antibodies with muscarinic cholinergic activity in human Chagas’ disease: pathological implications. Journal of the Autonomic Nervous System 47, 4552.Google Scholar
Goin, J. C., Borda, E. S., Auger, S., Storino, R. and Sterin-Borda, L. (1999). Cardiac M(2) muscarinic cholinoceptor activation by human chagasic autoantibodies: association with bradycardia. Heart 82, 273278.Google Scholar
Hernandez, C. C., Nascimento, J. H., Chaves, E. A., Costa, P. C., Masuda, M. O., Kurtenbach, E., Campos, D. E. C. A. C. and Gimenez, L. E. (2008). Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas’ disease. Journal of Receptor and Signal Transduction Research 28, 375401.CrossRefGoogle ScholarPubMed
Higuchi, M. L. (1995). [Chagas disease. importance of the parasite in the pathogenesis of the cardiac chronic disease.] Arquivos brasileiros de cardiologia 64, 251254.Google ScholarPubMed
Iwai, L. K., Juliano, M. A., Juliano, L., Kalil, J. and Cunha-Neto, E. (2005). T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. Journal of Autoimmunity 24, 111117.Google Scholar
Iwata, M., Yoshikawa, T., Baba, A., Anzai, T., Mitamura, H. and Ogawa, S. (2001). Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy. Journal of the American College of Cardiology 37, 418424.Google Scholar
Jahns, R., Boivin, V., Siegmund, C., Inselmann, G., Lohse, M. J. and Boege, F. (1999). Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure. Circulation 99, 649654.Google Scholar
Jahns, R., Boivin, V., Hein, L., Triebel, S., Angermann, C. E., Ertl, G. and Lohse, M. J. (2004). Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. Journal of Clinical Investigation 113, 14191429.Google Scholar
Kierszenbaum, F. (1985). Is there autoimmunity in Chagas disease? Parasitology Today 1, 46.CrossRefGoogle ScholarPubMed
Koberle, F. (1970). The causation and importance of nervous lesions in American trypanosomiasis. Bulletin of the World Health Organization 42, 739743.Google Scholar
Labovsky, V., Smulski, C. R., Gomez, K., Levy, G. and Levin, M. J. (2007). Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease. Clinical and Experimental Immunology 148, 440449.Google Scholar
Leon, J. S. and Engman, D. M. (2003). The significance of autoimmunity in the pathogenesis of Chagas heart disease. Frontiers in Bioscience 8, e315e322.Google Scholar
Marino, A. P., da Silva, A., dos Santos, P., Pinto, L. M., Gazzinelli, R. T., Teixeira, M. M. and Lannes-Vieira, J. (2004). Regulated on activation, normal T cell expressed and secreted (RANTES) antagonist (Met-RANTES) controls the early phase of Trypanosoma cruzi-elicited myocarditis. Circulation 110, 14431449.CrossRefGoogle ScholarPubMed
Medei, E. H., Nascimento, J. H., Pedrosa, R. C., Barcellos, L., Masuda, M. O., Sicouri, S., Elizari, M. V. and de Carvalho, A. C. (2008). Antibodies with beta-adrenergic activity from chronic chagasic patients modulate the QT interval and M cell action potential duration. Europace 10, 868876.CrossRefGoogle Scholar
Perez-Molina, J. A., Norman, F. and Lopez-Velez, R. (2012). Chagas disease in non-endemic countries: epidemiology, clinical presentation and treatment. Current Infectious Disease Report 14, 263274.Google Scholar
Prata, A. (2001). Clinical and epidemiological aspects of Chagas disease. Lancet Infectious Diseases 1, 92100.Google Scholar
Prata, A., Lopes, E. R. and Chapadeiro, E. (1986). [Characteristics of unexpected sudden death in Chagas disease.] Revista da Sociedade Brasileira de Medicina Tropical 19, 912.Google Scholar
Rassi, A. Jr., Rassi, A. and Little, W. C. (2000). Chagas’ heart disease. Clinical Cardiology 23, 883889.Google ScholarPubMed
Reis, D. D., Gazzinelli, R. T., Gazzinelli, G. and Colley, D. G. (1993). Antibodies to Trypanosoma cruzi express idiotypic patterns that can differentiate between patients with asymptomatic or severe Chagas’ disease. Journal of Immunology 150, 16111618.Google Scholar
Ribeiro, A. L., Moraes, R. S., Ribeiro, J. P., Ferlin, E. L., Torres, R. M., Oliveira, E. and Rocha, M. O. (2001). Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease. American Heart Journal 141, 260265.Google Scholar
Ribeiro, A. L., Gimenez, L. E., Hernandez, C. C., de Carvalho, A. C., Teixeira, M. M., Guedes, V. C., Barros, M. V., Lombardi, F. and Rocha, M. O. (2007). Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease. International Journal of Cardiology 117, 5963.Google Scholar
Ribeiro, A. L., de Carvalho, A. C., Lombardi, F., Talvani, A., Teixeira, M. M. and Rocha, M. O. (2010). In vivo inhibitory effect of anti-muscarinic autoantibodies on the parasympathetic function in Chagas disease. International Journal of Cardiology 145, 339340.Google Scholar
Rossi, M. A. (1991). Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy. Canadian Journal of Cardiology 7, 287294.Google Scholar
Schulze, W., Kunze, R. and Wallukat, G. (2005). Pathophysiological role of autoantibodies against G-protein-coupled receptors in the cardiovascular system. Experimental and Clinical Cardiology 10, 170172.Google Scholar
Silverio, J. C., Pereira, I. R., Cipitelli Mda, C., Vinagre, N. F., Rodrigues, M. M., Gazzinelli, R. T. and Lannes-Vieira, J. (2012). CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy. PLOS Pathogens 8, e1002645.Google Scholar
Sterin-Borda, L. and Borda, E. (2000). Role of neurotransmitter autoantibodies in the pathogenesis of chagasic peripheral dysautonomia. Annals of the New York Academy of Sciences 917, 273280.Google Scholar
Stork, S., Boivin, V., Horf, R., Hein, L., Lohse, M. J., Angermann, C. E. and Jahns, R. (2006). Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy. American Heart Journal 152, 697704.Google Scholar
Talvani, A., Rocha, M. O., Ribeiro, A. L., Borda, E., Sterin-Borda, L. and Teixeira, M. M. (2006). Levels of anti-M2 and anti-beta1 autoantibodies do not correlate with the degree of heart dysfunction in Chagas’ heart disease. Microbes and Infection 8, 24592464.Google Scholar
Thiers, C. A., Barbosa, J. L., Pereira Bde, B., Nascimento, E. M., Nascimento, J. H., Medei, E. H. and Pedrosa, R. C. (2012). Autonomic dysfunction and anti-M2 and anti-beta1 receptor antibodies in Chagas disease patients. Arquivos brasileiros de cardiologia 99, 732739.Google Scholar
Wallukat, G., Wollenberger, A., Morwinski, R. and Pitschner, H. F. (1995). Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops. Journal of Molecular and Cellular Cardiology 27, 397406.CrossRefGoogle ScholarPubMed
Williams-Blangero, S., Magalhaes, T., Rainwater, E., Blangero, J., Correa-Oliveira, R. and Vandeberg, J. L. (2007). Electrocardiographic characteristics in a population with high rates of seropositivity for Trypanosoma cruzi infection. American Journal of Tropical Medicine and Hygiene 77, 495499.Google Scholar
World Health Organization (2010). WHO Report on Chagas Disease. World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases. WHO, Geneva, Switzerland.Google Scholar