Bojic Lazar A, McLaren David G, Shah Vinit, Previs Stephen F, Johns Douglas G, Castro-Perez Jose M
Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Int J Mol Sci. 2014 Dec 15;15(12):23283-93. doi: 10.3390/ijms151223283.
The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.
动脉粥样硬化斑块的细胞、大分子和中性脂质组成已得到广泛表征。然而，尚未有关于动脉粥样硬化病变内主要脂质类别的全面脂质组学分析报道。本研究的目的是构建一个详细的脂质框架，以描述一种广泛使用的斑块进展临床前模型的动脉粥样硬化病变中的脂质。给雄性新西兰白兔喂食添加了0.5%胆固醇（HC）的常规饲料，持续12周，以诱导高胆固醇血症和动脉粥样硬化。我们使用超高效液相色谱（UPLC）和高分辨率质谱对喂食HC饮食的兔子分离出的斑块进行脂质组学分析，检测到了大多数主要脂质类别，包括：胆固醇酯、三酰甘油、磷脂酰胆碱、鞘磷脂、二酰甘油、脂肪酸、磷脂酰丝氨酸、溶血磷脂酰胆碱、神经酰胺、磷脂酰甘油、磷脂酰肌醇和磷脂酰乙醇胺。鉴于胆固醇酯、三酰甘油和磷脂酰胆碱占血浆总脂质的75%以上，我们特别关注了这些脂质脂肪酸组成的定性和定量评估。我们还发现鞘磷脂是病变内相对丰富的脂质类别，并比较了鞘磷脂与其前体磷脂酰胆碱的丰度。本文所呈现的研究是对动脉粥样硬化斑块脂质组进行全面表征的首次尝试。
