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基于血清代谢组学鉴定溶血磷脂酰胆碱和神经鞘脂类作为急性主动脉夹层的潜在生物标志物

Identification of Lysophosphatidylcholines and Sphingolipids as Potential Biomarkers for Acute Aortic Dissection via Serum Metabolomics.

机构信息

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Vascular Surgery Institute of Fudan University, Shanghai, China.

School of Pharmacy, Second Military Medical University, Shanghai, China.

出版信息

Eur J Vasc Endovasc Surg. 2019 Mar;57(3):434-441. doi: 10.1016/j.ejvs.2018.07.004. Epub 2018 Aug 4.

DOI:10.1016/j.ejvs.2018.07.004
PMID:30087010
Abstract

OBJECTIVES

Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD.

METHODS

Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis.

RESULTS

A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender.

CONCLUSIONS

The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.

摘要

目的

急性主动脉夹层(AAD)是一种严重的临床急症,死亡率高,早期易误诊。本研究旨在发现具有诊断 AAD 及区分 AAD 两型潜力的血清代谢组学标志物。

方法

本研究纳入 35 例 AAD 患者,包括 20 例 Stanford 型 A 及 15 例 Stanford 型 B,另纳入 20 例健康对照。所有 AAD 患者均于发病 72 h 内入院。采用超高效液相色谱-四极杆飞行时间质谱法检测血清代谢组学谱,主成分分析和偏最小二乘判别分析进行数据分析。

结果

最终筛选并鉴定出 17 种代谢物在对照组和 AAD 组之间存在差异,这些代谢物为溶血磷脂酰胆碱(LPC)和鞘脂类,包括神经酰胺、鞘氨醇、植鞘氨醇和神经酰胺。与健康对照组相比,Stanford 型 A 和 B 型 AAD 组患者的 LPC 水平均显著降低。有趣的是,仅在 Stanford 型 A 型 AAD 组患者中,鞘脂类包括神经酰胺、鞘氨醇和植鞘氨醇显著减少,而在 Stanford 型 B 型 AAD 组患者中未见减少。亚组分析显示,LPC 和鞘脂水平的变化与高血压或性别无关。

结论

本研究结果表明,AAD 患者的 LPC 和鞘脂明显改变,且 Stanford 型 A 型 AAD 患者中几种鞘脂类如神经酰胺、鞘氨醇和植鞘氨醇显著减少。这两类代谢物的组合可能作为 AAD 的潜在诊断标志物,并有助于区分 Stanford 型 A 和 Stanford 型 B。

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