Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling

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dc.creatorVanessa Pereira Teixeira
dc.creatorItamar Couto Guedes de Jesus
dc.creatorAnderson Kenedy Santos
dc.creatorMauro de Oliveira
dc.creatorRaphael Escorsim Szawka
dc.creatorHelio Salgado
dc.creatorMarco Antonio Máximo Prado
dc.creatorMaristela Poletini
dc.creatorSilvia Guatimosim
dc.creatorKiany Miranda
dc.creatorSergio Scalzo
dc.creatorCibele Rocha Resende
dc.creatorMário Morais Silva
dc.creatorGeisa C. S. V. Tezini
dc.creatorMarcos Melo
dc.creatorFernando Pedro Souza Neto
dc.creatorKaoma Silva
dc.date.accessioned2023-07-14T19:33:18Z
dc.date.accessioned2025-09-08T23:37:04Z
dc.date.available2023-07-14T19:33:18Z
dc.date.issued2021
dc.identifier.doihttps://doi.org/10.1152/ajpcell.00142.2020
dc.identifier.issn0363-6143
dc.identifier.urihttps://hdl.handle.net/1843/56256
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofAmerican Journal of Physiology-Cell Physiology
dc.rightsAcesso Restrito
dc.subjectCoração
dc.subjectHipertrofia
dc.subject.otherCardiac dysfunction
dc.subject.otherCardiomyocytes
dc.subject.otherCholinergic signaling
dc.subject.otherHypertrophy
dc.titleIncreased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling
dc.typeArtigo de periódico
local.citation.epageC612
local.citation.issue4
local.citation.spageC602
local.citation.volume320
local.description.resumoCholinesterase inhibitors are used in postmenopausal women for the treatment of neurodegenerative diseases. Despite their widespread use in the clinical practice, little is known about the impact of augmented cholinergic signaling on cardiac function under reduced estrogen conditions. To address this gap, we subjected a genetically engineered murine model of systemic vesicular acetylcholine transporter overexpression (Chat-ChR2) to ovariectomy and evaluated cardiac parameters. Left-ventricular function was similar between Chat-ChR2 and wild-type (WT) mice. Following ovariectomy, WT mice showed signs of cardiac hypertrophy. Conversely, ovariectomized (OVX) Chat-ChR2 mice evolved to cardiac dilation and failure. Transcript levels for cardiac stress markers atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were similarly upregulated in WT/OVX and Chat-ChR2/OVX mice. 17b-Estradiol (E2) treatment normalized cardiac parameters in Chat-ChR2/OVX to the Chat-ChR2/SHAM levels, providing a link between E2 status and the aggravated cardiac response in this model. To investigate the cellular basis underlying the cardiac alterations, ventricular myocytes were isolated and their cellular area and contractility were assessed. Myocytes from WT/OVX mice were wider than WT/SHAM, an indicative of concentric hypertrophy, but their fractional shortening was similar. Conversely, Chat-ChR2/OVX myocytes were elongated and presented contractile dysfunction. E2 treatment again prevented the structural and functional changes in Chat-ChR2/OVX myocytes. We conclude that hypercholinergic mice under reduced estrogen conditions do not develop concentric hypertrophy, a critical compensatory adaptation, evolving toward cardiac dilation and failure. This study emphasizes the importance of understanding the consequences of cholinesterase inhibition, used clinically to treat dementia, for cardiac function in postmenopausal women.
local.identifier.orcidhttps://orcid.org/0000-0002-2510-7125
local.identifier.orcidhttps://orcid.org/0000-0001-5532-9813
local.identifier.orcidhttps://orcid.org/0000-0002-6185-3491
local.identifier.orcidhttps://orcid.org/0000-0002-2639-3469
local.identifier.orcidhttps://orcid.org/0000-0002-3028-5778
local.identifier.orcidhttps://orcid.org/0000-0001-7351-5740
local.identifier.orcidhttps://orcid.org/0000-0001-8386-3722
local.identifier.orcidhttps://orcid.org/0000-0003-4917-889X
local.identifier.orcidhttps://orcid.org/0000-0002-7050-8040
local.identifier.orcidhttps://orcid.org/0000-0002-1496-878X
local.identifier.orcidhttps://orcid.org/0000-0002-5109-0654
local.identifier.orcidhttps://orcid.org/0000-0001-6458-842X
local.identifier.orcidhttps://orcid.org/0000-0003-4983-0681
local.identifier.orcidhttps://orcid.org/0000-0003-1990-5224
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA
local.publisher.initialsUFMG
local.url.externahttps://journals.physiology.org/doi/full/10.1152/ajpcell.00142.2020

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