Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.
Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.
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DOI：
10.3390/jcm9092915
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发表时间：
2020-09-10
影响因子：
3.9
通讯作者：
Connelly MA
中科院分区：
文献类型：
--
作者：
Bedi S;Garcia E;Jeyarajah EJ;Shalaurova I;Perez-Matos MC;Jiang ZG;Dullaart RPF;Matyus SP;Kirk WJ;Otvos JD;Davidson WS;Connelly MA
背景资料：具有异常组成的脂蛋白颗粒，如脂蛋白X（LP-X）和脂蛋白Z（LP-Z），已在阻塞性黄疸和胆汁淤积的病例中描述。研究目的是：（1）开发用于定量血浆/血清LP-Z颗粒的基于NMR的测定，（2）评价测定性能，（3）分离LP-Z颗粒并通过脂质组学和蛋白质组学分析表征它们，以及（4）定量患有各种肝病的受试者中的LP-Z。方法：评估测定性能的线性、灵敏度和精密度。质谱用于表征分离的LP-Z颗粒的蛋白质和脂质含量。结果：本法线性关系良好，精密度（2.5-6.3%）良好。脂质分析表明，LP-Z颗粒表现出较低的胆固醇酯和较高的游离胆固醇，胆汁酸，酰基肉毒碱，二酰基甘油酯，二己糖神经酰胺，溶血磷脂酰胆碱，磷脂酰胆碱，三酰基甘油酯，和脂肪酸比低密度脂蛋白（LDL）颗粒。蛋白质组学分析显示，LP-Z每个颗粒（如LDL）具有一个载脂蛋白B拷贝，但载脂蛋白（apo）A-I、apoC 3、apoA-IV和apoC 2较少，而补体C3较多。在健康志愿者或原发性胆管炎、原发性硬化性胆管炎、自身免疫性肝炎或2型糖尿病患者中未检测到LP-Z。LP-Z在一些但不是所有的高甘油三酯血症患者中检测到，并且在一些酒精性肝病患者中较高。结论：LP-Z与LDL的脂质和蛋白质含量存在显著差异。需要进一步的研究来充分了解胆汁淤积和酒精性肝病患者中LP-Z颗粒增强的病理生理原因。
Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. Methods: Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. Results: The assay showed good linearity and precision (2.5–6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. Conclusions: LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease.
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