人低密度脂蛋白的氧化脂质谱与其氧化程度有关。

Oxylipin profile of human low-density lipoprotein is dependent on its extent of oxidation.

机构信息

Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.

Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.

出版信息

Atherosclerosis. 2019 Sep;288:101-111. doi: 10.1016/j.atherosclerosis.2019.07.018. Epub 2019 Jul 18.

DOI:10.1016/j.atherosclerosis.2019.07.018

PMID:31352271

Abstract

BACKGROUND AND AIMS

Atherosclerosis is usually the underlying cause of heart attacks, strokes and peripheral vascular diseases - collectively known as cardiovascular diseases. Oxidation of low density lipoprotein (LDL) and its lipid content has an important role in the formation of lipid-laden atherosclerotic plaques. Not much is known about the impact of oxidative stress on bioactive oxylipin molecules present in LDL. The aim of this study is to understand the changes in oxylipin molecules present in LDL characterized by varying degrees of LDL oxidation.

METHODS

LDL was isolated from the pooled plasma of healthy normolipidemic volunteers and was subjected to in vitro copper-catalyzed oxidation for varying time intervals (0 h, 6 h, 12 h, 24 h and 30 h). At each time interval, oxylipins were isolated through solid phase extraction and quantified using a targeted LC/-MS/MS approach employing stable isotope dilution method.

RESULTS

Our results demonstrate that different forms of oxidized LDL (OxLDL) are characterized by specific oxylipin distribution and concentration. Compared to non-oxidized LDL, there is a significant increase in oxylipin generation (p ≤ 0.05) in OxLDL subjected to 12 h and 24 h of oxidation. Though linoleate derived oxylipins are the most abundant in OxLDL extracts, the concentration of particular oxylipin species differed with different degrees of oxidation. Specifically, two pro-inflammatory linoleate-derived triols, namely 9,10,13-triHOME and 9,12,13-triHOME, exhibited a concentration increase of ~25 fold in 12h-OxLDL compared to non-oxidized LDL. Moreover, Partial least squares Discriminant Analysis (PLS-DA) identified 10 oxylipins, primarily prostaglandins, which could serve as additional biomarkers for oxidative stress or cardiovascular risk assessment.

CONCLUSIONS

Our data suggests that oxidative stress induces profound changes in the oxylipin content of LDL and the pattern of change is based on the extent of oxidation.

摘要

背景与目的

动脉粥样硬化通常是心脏病发作、中风和外周血管疾病（统称为心血管疾病）的根本原因。低密度脂蛋白（LDL）的氧化及其脂质含量在富含脂质的动脉粥样硬化斑块的形成中起着重要作用。关于氧化应激对 LDL 中存在的生物活性氧化脂蛋白分子的影响，人们知之甚少。本研究旨在了解不同程度 LDL 氧化所导致的 LDL 中氧化脂蛋白分子的变化。

方法

从健康正常脂质志愿者的混合血浆中分离 LDL，并进行体外铜催化氧化，时间间隔分别为 0 小时、6 小时、12 小时、24 小时和 30 小时。在每个时间间隔，通过固相萃取分离氧化脂蛋白，并采用稳定同位素稀释法的靶向 LC/-MS/MS 方法进行定量。

结果

我们的结果表明，不同形式的氧化 LDL（OxLDL）具有特定的氧化脂蛋白分布和浓度特征。与未氧化的 LDL 相比，氧化 12 小时和 24 小时的 OxLDL 中氧化脂蛋白的生成显著增加（p≤0.05）。尽管亚油酸衍生的氧化脂蛋白在 OxLDL 提取物中最为丰富，但特定氧化脂蛋白的浓度因氧化程度不同而有所差异。具体而言，两种促炎的亚油酸衍生三醇，即 9,10,13-三 HOME 和 9,12,13-三 HOME，在 12h-OxLDL 中的浓度比未氧化的 LDL 增加了约 25 倍。此外，偏最小二乘判别分析（PLS-DA）鉴定出 10 种氧化脂蛋白，主要是前列腺素，它们可以作为氧化应激或心血管风险评估的附加生物标志物。