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血清非靶向脂质组学分析揭示亚临床冠状动脉疾病中磷脂代谢功能障碍。

Serum untargeted lipidomic profiling reveals dysfunction of phospholipid metabolism in subclinical coronary artery disease.

作者信息

Djekic Demir, Pinto Rui, Repsilber Dirk, Hyotylainen Tuulia, Henein Michael

机构信息

Department of Cardiology, School of Medical Sciences, Örebro University, Örebro, Sweden.

Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.

出版信息

Vasc Health Risk Manag. 2019 May 13;15:123-135. doi: 10.2147/VHRM.S202344. eCollection 2019.


DOI:10.2147/VHRM.S202344
PMID:31190850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6526169/
Abstract

Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates. We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach. We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG(49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC. In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.

摘要

胆固醇和三酰甘油(TGs)代谢紊乱会增加冠状动脉钙化(CAC)风险。然而,个体脂质种类与CAC的确切关系仍不明确。本研究旨在确定参与钙化过程的脂质谱紊乱情况,以尝试提出潜在的生物标志物候选物。我们研究了70例处于冠状动脉疾病中等风险的患者,这些患者已通过计算机断层扫描和阿加斯顿冠状动脉钙化评分(CACS)进行了冠状动脉钙化评估。患者被分为三组:无冠状动脉钙化(NCC;CACS:0;n = 26)、轻度冠状动脉钙化(MCC;CACS:1 - 250;n = 27)或重度冠状动脉钙化(SCC;CACS:>250;n = 17)。采用非靶向脂质组学方法,利用液相色谱 - 质谱联用技术分析患者的血清样本。我们在甘油olipid、甘油磷脂、鞘脂和甾醇脂质类别中鉴定出103种脂质。经过错误发现率校正后,与NCC相比,较高水平的磷脂酰胆碱(PC)(16:0/20:4)以及较低水平的PC(18:2/18:2)、PC(36:3)和磷脂酰乙醇胺(20:0/18:2)被确定为与SCC相关。三组之间个体TGs水平无显著差异;然而,脂质谱聚类显示,与NCC相比,SCC中饱和和单不饱和TGs水平有升高趋势。与MCC相比,SCC中TG(49:2)、TG(51:1)、TG(54:5)和TG(56:8)水平也有降低趋势。在本研究中,我们调查了冠状动脉钙化患者的脂质组。我们的结果表明,钙化过程可能与自噬功能障碍有关。本研究中揭示的脂质组学生物标志物可能有助于更好地评估亚临床冠状动脉疾病患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/c5391c39b7f7/VHRM-15-123-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/7be1a3dcf9ab/VHRM-15-123-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/07c94a9eeb34/VHRM-15-123-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/c5391c39b7f7/VHRM-15-123-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/7be1a3dcf9ab/VHRM-15-123-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/07c94a9eeb34/VHRM-15-123-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/6526169/c5391c39b7f7/VHRM-15-123-g0003.jpg

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本文引用的文献

[1]
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Eur J Prev Cardiol. 2018-8-10

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Int J Cardiol. 2016-11-1

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J Cell Physiol. 2016-10

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