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脂蛋白分离术患者的脂质组学分析方法

A lipidomic analysis approach in patients undergoing lipoprotein apheresis.

作者信息

Schmöcker C, Kassner U, Kiesler S, Bismarck M, Rothe M, Steinhagen-Thiessen E, Weylandt K H

机构信息

Medical Department, Division of Hepatology and Gastroenterology (including Metabolic Diseases), Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany; Department of Gastroenterology, Sana Klinikum Lichtenberg, Berlin, Germany.

Medical Department, Division of Hepatology and Gastroenterology (including Metabolic Diseases), Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany.

出版信息

Atherosclerosis. 2016 Jun;249:30-5. doi: 10.1016/j.atherosclerosis.2016.03.019. Epub 2016 Mar 19.

DOI:10.1016/j.atherosclerosis.2016.03.019
PMID:27062407
Abstract

Lipoprotein apheresis such as heparin-induced extracorporal LowDensityLipoprotein (LDL) Cholesterol precipitation (HELP) reduces apolipoprotein B-containing lipoproteins, most importantly low-density-lipoprotein (LDL), and lipoprotein (a) [Lp(a)]. It is used in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or progressive atherosclerotic disease in patients with elevated Lp(a). While lipid-lowering effects of lipoprotein apheresis are well-established, there are only sparse data regarding the effect of apheresis on individual omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA), such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could increase (AA) or decrease (EPA and DHA) cardiovascular risk. Here we analyzed different omega-6 and omega-3 fatty acids in the blood of patients undergoing a single HELP apheresis procedure using gas chromatography (GC). Furthermore, we assessed the effect of HELP treatment on formation of lipid metabolites and mediators arising from these polyunsaturated fatty acids in the plasma by LC/ESI-MS/MS. Lipoprotein apheresis reduced the concentrations of fatty acids analyzed in the plasma by 40-50%. This was similar for AA, EPA and DHA. The reduction in fatty acid plasma levels was similar to the reduction of total triglycerides. However there was a trend towards an increase of PUFA metabolites associated with platelet activation, such as 12-hydroxyeicosatetraenoic acid (12-HETE) and 14-hydroxydocosahexaenoic acid (14-HDHA). These data indicate that HELP apheresis could interfere with achieving higher levels of n-3 PUFA in the plasma. Lipid apheresis treatment might also increase the formation of potentially pro- as well as anti-inflammatory lipid mediators derived from AA or EPA and DHA.

摘要

脂蛋白分离术,如肝素诱导的体外低密度脂蛋白(LDL)胆固醇沉淀法(HELP),可降低含载脂蛋白B的脂蛋白,其中最重要的是低密度脂蛋白(LDL)和脂蛋白(a)[Lp(a)]。它用于患有动脉粥样硬化疾病以及治疗难治性高胆固醇血症的患者,或Lp(a)升高的进展性动脉粥样硬化疾病患者。虽然脂蛋白分离术的降脂效果已得到充分证实,但关于分离术对个体ω-6和ω-3多不饱和脂肪酸(n-6 PUFA和n-3 PUFA)的影响的数据却很少,比如花生四烯酸(AA)、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA),这些脂肪酸可能会增加(AA)或降低(EPA和DHA)心血管风险。在此,我们使用气相色谱法(GC)分析了接受单次HELP分离术的患者血液中的不同ω-6和ω-3脂肪酸。此外,我们通过液相色谱/电喷雾串联质谱法(LC/ESI-MS/MS)评估了HELP治疗对这些多不饱和脂肪酸在血浆中产生的脂质代谢产物和介质形成的影响。脂蛋白分离术使血浆中分析的脂肪酸浓度降低了40%-50%。AA、EPA和DHA的情况类似。脂肪酸血浆水平的降低与总甘油三酯的降低相似。然而,与血小板活化相关的PUFA代谢产物有增加的趋势,如12-羟基二十碳四烯酸(12-HETE)和14-羟基二十二碳六烯酸(14-HDHA)。这些数据表明,HELP分离术可能会干扰血浆中n-3 PUFA达到更高水平。脂质分离术治疗也可能会增加源自AA或EPA和DHA的潜在促炎和抗炎脂质介质的形成。

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