Sigma-1 receptor knockout
Sigma-1 receptor knockout
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Dong-Zhao
中科院分区：
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作者：
Jian-Zheng Yang;Kai-Kai Zhang1;Hong-Wu Shen;Dong-Zhao
Introduction: Heart failure (HF) is usually the end stage of the continuum of various .cardiovascular diseases. However, the mechanism underlying the progression and .development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is .a non-opioid transmembrane receptor implicated in many diseases, including HF. .However, the role of Sigmar1 in HF has not been fully elucidated..Methods: In this study, we used isoproterenol (ISO) to induce HF in wildtype (WT) and Sigmar1 knockout (Sigmar1−/−) mice. Multi-omic analysis, .including microbiomics, metabolomics and transcriptomics, was employed to .comprehensively evaluate the role of Sigmar1 in HF..Results: Compared with the WT-ISO group, Sigmar1−/− aggravated ISO-induced .HF, including left ventricular systolic dysfunction and ventricular remodeling. .Moreover, Sigmar1−/− exacerbated ISO-induced gut microbiota dysbiosis, which .was demonstrated by the lower abundance of probiotics g_Akkermansia and .g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_.Oscillospiraceae and Allobaculum. Furthermore, differential metabolites .among WT-Control, WT-ISO and Sigmar−/−-ISO groups were mainly enriched .in bile secretion, tryptophan metabolism and phenylalanine metabolism, which .presented a close association with microbial dysbiosis. Corresponding with the .exacerbation of the microbiome, the inflammation-related NOD-like receptor .signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway .were activated in the heart tissues..Conclusion: Taken together, this study provides evidence that a Sigmar1 knockout .disturbs the gut microbiota and remodels the serum metabolome, which may .exacerbate HF by stimulating heart inflammation.
