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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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