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Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model
Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604683/ https://www.ncbi.nlm.nih.gov/pubmed/37893138 http://dx.doi.org/10.3390/biomedicines11102766 |
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author | Liu, Yi Chen, Qing Yang, Jian-Zheng Li, Xiu-Wen Chen, Li-Jian Zhang, Kai-Kai Liu, Jia-Li Li, Jia-Hao Hsu, Clare Chen, Long Zeng, Jia-Hao Wang, Qi Zhao, Dong Xu, Jing-Tao |
author_facet | Liu, Yi Chen, Qing Yang, Jian-Zheng Li, Xiu-Wen Chen, Li-Jian Zhang, Kai-Kai Liu, Jia-Li Li, Jia-Hao Hsu, Clare Chen, Long Zeng, Jia-Hao Wang, Qi Zhao, Dong Xu, Jing-Tao |
author_sort | Liu, Yi |
collection | PubMed |
description | Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS. |
format | Online Article Text |
id | pubmed-10604683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106046832023-10-28 Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model Liu, Yi Chen, Qing Yang, Jian-Zheng Li, Xiu-Wen Chen, Li-Jian Zhang, Kai-Kai Liu, Jia-Li Li, Jia-Hao Hsu, Clare Chen, Long Zeng, Jia-Hao Wang, Qi Zhao, Dong Xu, Jing-Tao Biomedicines Article Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS. MDPI 2023-10-12 /pmc/articles/PMC10604683/ /pubmed/37893138 http://dx.doi.org/10.3390/biomedicines11102766 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yi Chen, Qing Yang, Jian-Zheng Li, Xiu-Wen Chen, Li-Jian Zhang, Kai-Kai Liu, Jia-Li Li, Jia-Hao Hsu, Clare Chen, Long Zeng, Jia-Hao Wang, Qi Zhao, Dong Xu, Jing-Tao Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title | Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title_full | Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title_fullStr | Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title_full_unstemmed | Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title_short | Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model |
title_sort | multi-omics analysis reveals the role of sigma-1 receptor in a takotsubo-like cardiomyopathy model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604683/ https://www.ncbi.nlm.nih.gov/pubmed/37893138 http://dx.doi.org/10.3390/biomedicines11102766 |
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