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http://hdl.handle.net/1843/56256| Tipo: | Artigo de Periódico |
| Título: | Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling |
| Autor(es): | Vanessa Pereira Teixeira Itamar Couto Guedes de Jesus Anderson Kenedy Santos Mauro de Oliveira Raphael Escorsim Szawka Helio Salgado Marco Antonio Máximo Prado Maristela Poletini Silvia Guatimosim Kiany Miranda Sergio Scalzo Cibele Rocha Resende Mário Morais Silva Geisa C. S. V. Tezini Marcos Melo Fernando Pedro Souza Neto Kaoma Silva |
| Resumo: | Cholinesterase 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. |
| Assunto: | Coração Hipertrofia |
| Idioma: | por |
| País: | Brasil |
| Editor: | Universidade Federal de Minas Gerais |
| Sigla da Instituição: | UFMG |
| Departamento: | ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA |
| Tipo de Acesso: | Acesso Restrito |
| Identificador DOI: | https://doi.org/10.1152/ajpcell.00142.2020 |
| URI: | http://hdl.handle.net/1843/56256 |
| Data do documento: | 2021 |
| metadata.dc.url.externa: | https://journals.physiology.org/doi/full/10.1152/ajpcell.00142.2020 |
| metadata.dc.relation.ispartof: | American Journal of Physiology-Cell Physiology |
| Aparece nas coleções: | Artigo de Periódico |
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