PDF(Pubmed)
Abstract：
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.
摘要：
Takotsubo综合征（TTS）是一种压力诱发的心肌病，由于极端的身体或情绪压力，突然出现胸痛，呼吸困难和心脏功能障碍。sigma-1受体（Sigmar1）是一种配体依赖性分子伴侣，据推测参与与心血管疾病相关的各种过程。然而,Sigmar1在TTS中的作用仍未解决。在这项研究中,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发育中的参与。我们的结果显示，Sigmar1基因敲除会加剧心脏功能障碍，与野生型模型相比，射血分数（EF）和缩短分数（FS）显着降低。就肠道微生物组而言，我们观察到Firmicutes和拟杆菌比例的调节；益生菌乳酸菌生长的抑制；以及病原菌种类的增加，如Colidextribacter。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几个信号通路中起作用。包括MAPK,HIF-1，钙信号，和凋亡途径，这可能在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，这种受体可能代表了TTS的有希望的治疗靶标。
