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

Abstract 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 re...

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Autores principales:	Robson Luiz Bandoni, Pamela Nithzi Bricher Choque, Humberto Dellê, Tercio Lemos de Moraes, Maria Helena Mattos Porter, Bruno Durante da Silva, Gizele Alves Neves, Maria-Claudia Irigoyen, Kátia De Angelis, Valentin A. Pavlov, Luis Ulloa, Fernanda Marciano Consolim-Colombo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f027e15a5877408e87e0c6e3edf1bfe2
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spelling	oai:doaj.org-article:f027e15a5877408e87e0c6e3edf1bfe22021-12-02T16:51:31ZCholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats10.1038/s41598-021-89104-82045-2322https://doaj.org/article/f027e15a5877408e87e0c6e3edf1bfe22021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89104-8https://doaj.org/toc/2045-2322Abstract 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.Robson Luiz BandoniPamela Nithzi Bricher ChoqueHumberto DellêTercio Lemos de MoraesMaria Helena Mattos PorterBruno Durante da SilvaGizele Alves NevesMaria-Claudia IrigoyenKátia De AngelisValentin A. PavlovLuis UlloaFernanda Marciano Consolim-ColomboNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robson Luiz Bandoni Pamela Nithzi Bricher Choque Humberto Dellê Tercio Lemos de Moraes Maria Helena Mattos Porter Bruno Durante da Silva Gizele Alves Neves Maria-Claudia Irigoyen Kátia De Angelis Valentin A. Pavlov Luis Ulloa Fernanda Marciano Consolim-Colombo Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
description	Abstract 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.
format	article
author	Robson Luiz Bandoni Pamela Nithzi Bricher Choque Humberto Dellê Tercio Lemos de Moraes Maria Helena Mattos Porter Bruno Durante da Silva Gizele Alves Neves Maria-Claudia Irigoyen Kátia De Angelis Valentin A. Pavlov Luis Ulloa Fernanda Marciano Consolim-Colombo
author_facet	Robson Luiz Bandoni Pamela Nithzi Bricher Choque Humberto Dellê Tercio Lemos de Moraes Maria Helena Mattos Porter Bruno Durante da Silva Gizele Alves Neves Maria-Claudia Irigoyen Kátia De Angelis Valentin A. Pavlov Luis Ulloa Fernanda Marciano Consolim-Colombo
author_sort	Robson Luiz Bandoni
title	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_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_sort	cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f027e15a5877408e87e0c6e3edf1bfe2
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Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats

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