UMR 1280 PHAN, INRA, CHU Hôtel Dieu, HNB1, Nantes, France.
CRNHO, West Human Nutrition Research Center, Nantes, France.
Cardiovasc Drugs Ther. 2017 Jun;31(3):269-279. doi: 10.1007/s10557-017-6737-y.
Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment.
Eight hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS) was used in mass spectrometry energy mode (HRMS) combined with ion mobility spectrometry to characterize the plasma and very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The accuracy and precision of the method were validated on plasma samples.
Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a multivariate analysis revealed a significant increase of lysophosphatidylcholine (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG 16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22:3) in HDL and LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL.
This lipidomic strategy characterized new specific lipid markers likely to be involved in the effect of ERN on cardiovascular risk opening a new strategy to analyze randomized controlled with this treatment.
NCT01216956.
血浆中高浓度的三酰甘油和低浓度的高密度脂蛋白胆固醇（HDL-C）与心血管事件的增加有关。烟酸缓释剂（ERN）已被证明可降低血浆三酰甘油和总胆固醇水平，但也可显著增加高密度脂蛋白胆固醇（HDL-C）。目前尚无关于 ERN 对不同种类的三酰甘油、胆固醇酯和磷脂的影响的数据。在这项研究中，我们应用一种非靶向脂质组学方法来研究接受 ERN 或安慰剂治疗的高甘油三酯血症患者的血浆和脂蛋白脂质谱，以确定与这种治疗相关的新脂质标志物。
8 名高甘油三酯血症患者参与了一项交叉随机试验，接受 ERN 治疗 8 周，每天 2g ERN 或安慰剂。采用超高效液相色谱（UPLC）与高分辨率质谱（HRMS）联用，在质谱能量模式（HRMS）下结合离子淌度谱对血浆和极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的脂质组进行了分析。该方法在血浆样品上的准确性和精密度进行了验证。
与安慰剂相比，在使用 UPLC-ESI-HRMS 鉴定的 155 种血浆脂质中，多元分析显示，在用 ERN 治疗后，溶血磷脂酰胆碱（LPC 20:5）显著增加，磷脂酰乙醇胺（PE 16:0/22:3）和鞘磷脂（SM d18:1/22:0）显著减少，三酰甘油（TG 16:0/16:1/18:2）减少。对脂蛋白中这些脂质的分析显示，HDL 中的 LPC（20:5）增加，HDL 和 LDL 中的 PE（16:0/22:3）减少，VLDL 和 LDL 中的 SM（d18:1/22:0）减少，VLDL 中的 TG（16:0/16:1/18:2）减少。
这种脂质组学策略鉴定了新的特定脂质标志物，这些标志物可能与 ERN 对心血管风险的作用有关，为分析这种治疗的随机对照试验开辟了新的策略。
NCT01216956。
