Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions
Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions
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DOI：
10.1194/jlr.m019174
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发表时间：
2011-11-01
影响因子：
6.5
通讯作者：
Murphy, Robert C.
中科院分区：
文献类型：
--
作者：
Hutchins, Patrick M.;Moore, Ernest E.;Murphy, Robert C.
尽管通过不同的实验治疗(如乙酰化)使低密度脂蛋白成为前动脉粥样硬化，但驱动低密度脂蛋白在体内转化的确切结构变化仍然是个谜。在许多假设的氧化修饰目标中，胆固醇酯(CE)就是其中之一。这种中性脂质家族携带高度不饱和的脂肪酰基，是低密度脂蛋白颗粒和动脉粥样硬化斑块的主要成分。利用串联质谱仪(MS/MS)揭示了人体周围血管病变中丰富多样的氧化CE(OxCE)，包括新的氧化产物。这些oxCE物种占总CE池的40%，其中胆固醇亚油酸酯被氧化的程度最大。成像质谱学研究表明，oxCE与未经修饰的CE和三酰甘油酯(TAG)一起完全局限于斑块内。有趣的是，我们没有发现TAG氧化的证据，尽管有丰富的多不饱和物种。15-脂氧合酶(15-LO)是CE氧化中经常使用的一种酶，它催化氧化胆固醇亚油酸酯，最初会产生区域和立体特异性产物。对人类动脉粥样硬化症中完整的胆固醇羟基十八碳二烯酸异构体的分析显示，没有区域或立体特异性，这表明15-LO要么不是oxCE的主要来源，要么是非酶过程侵蚀了任何产物特异性。电喷雾MS/MS显示人类外周血管病变中胆固醇酯的广泛和非特异性氧化。J.Lipid Res.2011年。52：2070-2083。
Although LDL is rendered proatherogenic by various experimental treatments (e. g., acetylation), the exact structural changes that drive LDL transformation in vivo remain enigmatic. Among the many hypothesized targets of oxidative modification are cholesterol esters (CE). This family of neutral lipids, which carries a highly unsaturated pool of fatty acyl groups, is the main component of both LDL particles and atherosclerotic plaques. Tandem mass spectrometry (MS/MS) was employed to reveal abundant and diverse oxidized CEs (oxCE), including novel oxidation products, within human peripheral vascular lesions. These oxCE species composed up to 40% of the total CE pool, with cholesteryl linoleate being oxidized to the greatest extent. Imaging mass spectrometry studies showed that oxCE was entirely confined within the plaque, along with unmodified CE and triacylglyceride (TAG). Interestingly, we found no evidence for TAG oxidation, although polyunsaturated species were abundant. Enzymatic oxidation of cholesteryl linoleate by 15-lipoxygenase (15-LO), an enzyme often invoked in CE oxidation, initially results in a regio- and stereospecific product. Analysis of intact cholesteryl hydroxyoctadecadienoate isomers in human atheromata revealed no regio- or stereospecificity, indicating 15-LO was either not a major source of oxCE or nonenzymatic processes had eroded any product specificity.-Hutchins, P. M., E. E. Moore, and R. C. Murphy. Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions. J. Lipid Res. 2011. 52: 2070-2083.