%0 Journal Article
%T Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model.
%A Liu Y
%A Chen Q
%A Yang JZ
%A Li XW
%A Chen LJ
%A Zhang KK
%A Liu JL
%A Li JH
%A Hsu C
%A Chen L
%A Zeng JH
%A Wang Q
%A Zhao D
%A Xu JT
%J Biomedicines
%V 11
%N 10
%D 2023 Oct 12
%M 37893138
%F 4.757
%R 10.3390/biomedicines11102766
%X 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.