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Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidate...

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Autores principales: Rodríguez-Angulo, Héctor O., Toro-Mendoza, Jhoan, Marques, Juan A., Concepción, Juan L., Bonfante-Cabarcas, Rafael, Higuerey, Yoliver, Thomas, Luz E., Balzano-Nogueira, Leandro, López, José R., Mijares, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315581/
https://www.ncbi.nlm.nih.gov/pubmed/25647069
http://dx.doi.org/10.1371/journal.pntd.0003512
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author Rodríguez-Angulo, Héctor O.
Toro-Mendoza, Jhoan
Marques, Juan A.
Concepción, Juan L.
Bonfante-Cabarcas, Rafael
Higuerey, Yoliver
Thomas, Luz E.
Balzano-Nogueira, Leandro
López, José R.
Mijares, Alfredo
author_facet Rodríguez-Angulo, Héctor O.
Toro-Mendoza, Jhoan
Marques, Juan A.
Concepción, Juan L.
Bonfante-Cabarcas, Rafael
Higuerey, Yoliver
Thomas, Luz E.
Balzano-Nogueira, Leandro
López, José R.
Mijares, Alfredo
author_sort Rodríguez-Angulo, Héctor O.
collection PubMed
description RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.
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spelling pubmed-43155812015-02-13 Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts Rodríguez-Angulo, Héctor O. Toro-Mendoza, Jhoan Marques, Juan A. Concepción, Juan L. Bonfante-Cabarcas, Rafael Higuerey, Yoliver Thomas, Luz E. Balzano-Nogueira, Leandro López, José R. Mijares, Alfredo PLoS Negl Trop Dis Research Article RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients. Public Library of Science 2015-02-03 /pmc/articles/PMC4315581/ /pubmed/25647069 http://dx.doi.org/10.1371/journal.pntd.0003512 Text en © 2015 Rodríguez-Angulo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rodríguez-Angulo, Héctor O.
Toro-Mendoza, Jhoan
Marques, Juan A.
Concepción, Juan L.
Bonfante-Cabarcas, Rafael
Higuerey, Yoliver
Thomas, Luz E.
Balzano-Nogueira, Leandro
López, José R.
Mijares, Alfredo
Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title_full Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title_fullStr Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title_full_unstemmed Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title_short Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts
title_sort evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by t. cruzi in isolated rat hearts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315581/
https://www.ncbi.nlm.nih.gov/pubmed/25647069
http://dx.doi.org/10.1371/journal.pntd.0003512
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