Rasmiena Aliki A, Barlow Christopher K, Ng Theodore W, Tull Dedreia, Meikle Peter J
Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Victoria, Australia.
Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Biochim Biophys Acta. 2016 Feb;1861(2):69-77. doi: 10.1016/j.bbalip.2015.11.002. Epub 2015 Nov 10.
Oxidised low density lipoprotein (oxLDL) contributes to atherosclerosis, whereas high density lipoprotein (HDL) is known to be atheroprotective due, at least in part, to its ability to remove oxidised lipids from oxLDL. The molecular details of the lipid transfer process are not fully understood. We aimed to identify major oxidised lipid species of oxLDL and investigate their transfer upon co-incubation with HDL with varying levels of oxidation.
A total of 14 major species of oxidised phosphatidylcholine and oxidised cholesteryl ester from oxLDL were identified using an untargeted mass spectrometry approach. HDL obtained from pooled plasma of normolipidemic subjects (N=5) was oxidised under mild and heavy oxidative conditions. Non-oxidised (native) HDL and oxidised HDL were co-incubated with oxLDL, re-isolated and lipidomic analysis was performed. Lipoprotein surface lipids, oxidised phosphatidylcholines and oxidised cholesterols (7-ketocholesterol and 7β-hydroxycholesterol), but not internal oxidised cholesteryl esters, were effectively transferred to native HDL. Saturated and monounsaturated lyso-phosphatidylcholines were also transferred from the oxLDL to native HDL. These processes were attenuated when HDL was oxidised under mild and heavy oxidative conditions. The impaired capacities were accompanied by an increase in a ratio of sphingomyelin to phosphatidylcholine and a reduction in phosphatidylserine content in oxidised HDL, both of which are potentially important regulators of the oxidised lipid transfer capacity of HDL.
Our study has revealed the differential transfer efficiency of surface and internal oxidised lipids from oxLDL and their acceptance onto HDL. These capacities were modulated when HDL was itself oxidised.
氧化型低密度脂蛋白（oxLDL）会促进动脉粥样硬化，而高密度脂蛋白（HDL）已知具有抗动脉粥样硬化作用，至少部分原因是其能够从oxLDL中清除氧化脂质。脂质转移过程的分子细节尚未完全明确。我们旨在鉴定oxLDL的主要氧化脂质种类，并研究其与不同氧化水平的HDL共同孵育时的转移情况。
采用非靶向质谱方法鉴定出oxLDL中总共14种主要的氧化磷脂酰胆碱和氧化胆固醇酯种类。从血脂正常受试者（N = 5）的混合血浆中获取的HDL在轻度和重度氧化条件下进行氧化处理。将未氧化（天然）的HDL和氧化后的HDL与oxLDL共同孵育，重新分离后进行脂质组学分析。脂蛋白表面脂质、氧化磷脂酰胆碱和氧化胆固醇（7-酮胆固醇和7β-羟基胆固醇），而非内部氧化胆固醇酯，有效地转移至天然HDL。饱和和单不饱和溶血磷脂酰胆碱也从oxLDL转移至天然HDL。当HDL在轻度和重度氧化条件下氧化时，这些过程会减弱。能力受损伴随着氧化HDL中鞘磷脂与磷脂酰胆碱比例的增加以及磷脂丝氨酸含量的减少，这两者均可能是HDL氧化脂质转移能力的重要潜在调节因子。
我们的研究揭示了oxLDL表面和内部氧化脂质的差异转移效率以及它们在HDL上的接受情况。当HDL自身被氧化时，这些能力会受到调节。
