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
Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
Key Laboratory of Evidence Science, China University of Political Science and Law, Ministry of Education, Beijing 100088, China.
Biomedicines. 2023 Oct 12;11(10):2766. doi: 10.3390/biomedicines11102766.
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.
应激性心肌病（TTS）是一种由应激诱发的心肌病，因极端的身体或情绪应激而突然出现胸痛、呼吸困难及心脏功能障碍。σ-1受体（Sigmar1）是一种配体依赖性分子伴侣，据推测参与了与心血管疾病相关的各种过程。然而，Sigmar1在TTS中的作用仍未明确。在本研究中，我们使用野生型和Sigmar1基因敲除小鼠建立了TTS小鼠模型，以研究Sigmar1在TTS发展过程中的作用。我们的结果显示，与野生型模型相比，Sigmar1基因敲除加剧了心脏功能障碍，射血分数（EF）和缩短分数（FS）显著降低。在肠道微生物群方面，我们观察到厚壁菌门和拟杆菌门比例的调节；益生菌乳酸杆菌生长受到抑制；以及致病性细菌种类如柯氏杆菌的增加。代谢组学和转录组学分析进一步表明，Sigmar1在调节色氨酸代谢和包括丝裂原活化蛋白激酶（MAPK）、缺氧诱导因子-1（HIF-1）、钙信号传导和凋亡途径在内的多种信号通路中发挥作用，这些通路可能在TTS发病机制中至关重要。这些发现为Sigmar1在TTS中的功能提供了有价值的见解，并且该受体可能是TTS一个有前景的治疗靶点。
