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采用高分辨率模式的液相色谱-串联质谱法分析血清磷脂谱以评估动脉粥样硬化患者。

Analysis of serum phospholipid profiles by liquid chromatography-tandem mass spectrometry in high resolution mode for evaluation of atherosclerotic patients.

作者信息

Calderón-Santiago M, Priego-Capote F, Galache-Osuna J G, Luque de Castro M D

机构信息

Department of Analytical Chemistry, Annex Marie Curie Building, Campus of Rabanales, University of Córdoba, E-14071 Córdoba, Spain; Institute of Biomedical Research Maimónides (IMIBIC), Reina Sofía Hospital, University of Córdoba, E-14071 Córdoba, Spain.

Department of Analytical Chemistry, Annex Marie Curie Building, Campus of Rabanales, University of Córdoba, E-14071 Córdoba, Spain; Institute of Biomedical Research Maimónides (IMIBIC), Reina Sofía Hospital, University of Córdoba, E-14071 Córdoba, Spain.

出版信息

J Chromatogr A. 2014 Dec 5;1371:154-62. doi: 10.1016/j.chroma.2014.10.052. Epub 2014 Oct 24.

DOI:10.1016/j.chroma.2014.10.052
PMID:25456593
Abstract

Atherosclerosis is one of the most frequent etiology for myocardial infarction and death. It is also the main cause of angina pectoris, a perceived symptom that results of a mismatch between myocardial supply and demand, caused by the partial obstruction of the arteries. The correct diagnosis of atherosclerosis can led to a reduction of mortality. In this research, the phospholipids profile of serum samples from patients diagnosed with stable angina and non-ST elevation myocardial infarction (NSTEMI) or unstable angina was obtained by selective solid-phase extraction (SPE) and subsequent LC-QTOF MS/MS analysis in high resolution mode. Comparative statistical analysis allowed finding four potential markers to discriminate between stable angina and NSTEMI/unstable angina: lysoPC(20:5), PC(18:1/18:2), PC(18:0/20:4) and SM(d18:2/14:0). The panel generated by multivariate ROC analysis by combination of the four compounds provided a disease prediction capability in the training set of 70.7 and 66.0% for stable angina and NSTEMI patients, respectively. On the other hand, external validation by application to an independent cohort improved the predictive power for angina stable patients (92.3%), while this was slightly decreased up to 50.0% for NSTEMI/unstable angina patients. In this way, LC-QTOF MS/MS has shown to be a useful strategy for phospholipid profiling in serum and development of tools to aid in clinical diagnostic.

摘要

动脉粥样硬化是心肌梗死和死亡最常见的病因之一。它也是心绞痛的主要原因,心绞痛是一种感知症状,由动脉部分阻塞导致心肌供需不匹配引起。动脉粥样硬化的正确诊断可降低死亡率。在本研究中,通过选择性固相萃取(SPE)以及随后的高分辨率模式下的液相色谱-四极杆飞行时间串联质谱(LC-QTOF MS/MS)分析,获得了诊断为稳定型心绞痛和非ST段抬高型心肌梗死(NSTEMI)或不稳定型心绞痛患者的血清样本磷脂谱。比较统计分析发现了四种潜在标志物,可区分稳定型心绞痛与NSTEMI/不稳定型心绞痛:溶血磷脂酰胆碱(lysoPC(20:5))、磷脂酰胆碱(PC(18:1/18:2))、磷脂酰胆碱(PC(18:0/20:4))和鞘磷脂(SM(d18:2/14:0))。由这四种化合物组合通过多变量ROC分析生成的面板,在训练集中对稳定型心绞痛和NSTEMI患者的疾病预测能力分别为70.7%和66.0%。另一方面,应用于独立队列的外部验证提高了对稳定型心绞痛患者的预测能力(92.3%),而对NSTEMI/不稳定型心绞痛患者的预测能力略有下降,降至50.0%。通过这种方式,LC-QTOF MS/MS已被证明是血清磷脂谱分析以及开发辅助临床诊断工具的有用策略。

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