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Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats

The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses a...

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Autores principales: Bandoni, Robson Luiz, Bricher Choque, Pamela Nithzi, Dellê, Humberto, de Moraes, Tercio Lemos, Porter, Maria Helena Mattos, da Silva, Bruno Durante, Neves, Gizele Alves, Irigoyen, Maria-Claudia, De Angelis, Kátia, Pavlov, Valentin A., Ulloa, Luis, Consolim-Colombo, Fernanda Marciano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099899/
https://www.ncbi.nlm.nih.gov/pubmed/33953291
http://dx.doi.org/10.1038/s41598-021-89104-8
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author Bandoni, Robson Luiz
Bricher Choque, Pamela Nithzi
Dellê, Humberto
de Moraes, Tercio Lemos
Porter, Maria Helena Mattos
da Silva, Bruno Durante
Neves, Gizele Alves
Irigoyen, Maria-Claudia
De Angelis, Kátia
Pavlov, Valentin A.
Ulloa, Luis
Consolim-Colombo, Fernanda Marciano
author_facet Bandoni, Robson Luiz
Bricher Choque, Pamela Nithzi
Dellê, Humberto
de Moraes, Tercio Lemos
Porter, Maria Helena Mattos
da Silva, Bruno Durante
Neves, Gizele Alves
Irigoyen, Maria-Claudia
De Angelis, Kátia
Pavlov, Valentin A.
Ulloa, Luis
Consolim-Colombo, Fernanda Marciano
author_sort Bandoni, Robson Luiz
collection PubMed
description The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3(+) and CD4(+) lymphocytes, and CD68(+) and CD206(+) macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4(+) lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.
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spelling pubmed-80998992021-05-07 Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats Bandoni, Robson Luiz Bricher Choque, Pamela Nithzi Dellê, Humberto de Moraes, Tercio Lemos Porter, Maria Helena Mattos da Silva, Bruno Durante Neves, Gizele Alves Irigoyen, Maria-Claudia De Angelis, Kátia Pavlov, Valentin A. Ulloa, Luis Consolim-Colombo, Fernanda Marciano Sci Rep Article The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3(+) and CD4(+) lymphocytes, and CD68(+) and CD206(+) macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4(+) lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8099899/ /pubmed/33953291 http://dx.doi.org/10.1038/s41598-021-89104-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bandoni, Robson Luiz
Bricher Choque, Pamela Nithzi
Dellê, Humberto
de Moraes, Tercio Lemos
Porter, Maria Helena Mattos
da Silva, Bruno Durante
Neves, Gizele Alves
Irigoyen, Maria-Claudia
De Angelis, Kátia
Pavlov, Valentin A.
Ulloa, Luis
Consolim-Colombo, Fernanda Marciano
Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title_full Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title_fullStr Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title_full_unstemmed Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title_short Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
title_sort cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099899/
https://www.ncbi.nlm.nih.gov/pubmed/33953291
http://dx.doi.org/10.1038/s41598-021-89104-8
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