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利用非靶向代谢组学鉴定新型心血管疾病相关代谢物。

Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics.

机构信息

King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Biol Chem. 2021 Jan 20;402(6):749-757. doi: 10.1515/hsz-2020-0331. Print 2021 May 26.

Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and 1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, -acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

摘要

心血管疾病 (CVD) 仍然是全球发病率和死亡率的主要原因。CVD 的早期诊断可为合理管理和更好的临床结果提供机会,同时还可防止疾病进一步进展。在本研究中,我们使用非靶向代谢组学方法来确定与 CVD 密切相关的可能代谢物,这些代谢物可以作为治疗靶点或与疾病相关的代谢物。我们鉴定了 26 种在 CVD 患者血清中存在差异的合理调整的独特代谢物,其中 15 种具有统计学意义。在这些代谢物中,我们发现了一些以前没有报道与 CVD 直接相关的新型代谢物,如 UDP-l-鼠李糖和 1-乙酰亚精胺。此外,我们还发现一些代谢物,如乙醇酰胺、茄碱、二甲基精氨酸、-乙酰-l-酪氨酸,可以作为 CVD 的鉴别标志物。代谢物整合途径富集分析显示,CVD 患者中存在各种重要代谢途径的富集,如组氨酸代谢、甲基组氨酸代谢、肉碱合成以及精氨酸和脯氨酸代谢。我们的研究为了解鉴定出的独特代谢物的病理生理作用和影响提供了很好的机会,并可以推断为特定的 CVD 特异性代谢物。

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