Ćwiklińska Agnieszka, Gliwińska Anna, Senderowska Zuzanna, Kortas-Stempak Barbara, Kuchta Agnieszka, Dąbkowski Kamil, Jankowski Maciej
Department of Clinical Chemistry, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland.
Department of Clinical Chemistry, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland.
Chem Phys Lipids. 2016 Feb;195:63-70. doi: 10.1016/j.chemphyslip.2015.12.007. Epub 2016 Jan 3.
Lipoprotein lipase (LPL)-mediated triacylglycerol (TAG) hydrolysis in very low density lipoprotein (VLDL) is accompanied by the release of surface material containing phospholipids (PL), free cholesterol (FC) and apolipoproteins, E (apoE) and Cs (apoCII, apoCIII). The released molecules are accepted by high density lipoprotein (HDL), and new HDL-sized apoE-containing particles are also generated. A decrease in the number of HDL particles or abnormalities in their structure is associated with unfavourable changes in the features of VLDL remnants. Phosphatidylcholine liposomes (PC-L) can also act as acceptors of surface material components released from lipoproteins. Thus, the aim of this study was to assess the impact of liposomes on compositional changes of VLDL during its LPL-mediated lipolysis. VLDL isolated from human sera was incubated with LPL (LPL:VLDLTAG; 24 μg/ml:90 mg/dl) and/or PC-L (VLDLPL:PC-LPL; 1:30 weight ratio). After incubation (2h, 37 °C) VLDL was separated from other reaction products, and VLDL lipid and apolipoprotein content were analysed. Newly generated HDL-sized apoE-containing lipoproteins were separated by two-dimensional non-denaturing gradient gel electrophoresis (2D-PAGGE). The reaction of VLDL with PC-L in the presence or absence of LPL significantly affected the VLDL composition. The ratio of core (TAG+cholesteryl ester) to surface (PL+FC) lipids in VLDL decreased 1.8-fold with PC-L, 1.2-fold with LPL and 3-fold with PC-L+LPL. The reaction with PC-L and PC-L+LPL caused a 3.7-fold and 3.2-fold decrease of apoCs/apoE average weight ratio, respectively. Compositional changes in VLDL under the influence of PC-L were accompanied by an increase in the efficiency of VLDL lipolysis and the generation of apoE-containing HDL-sized particles, heterogeneous in size (from ∼ 9 to ∼ 18.8 nm) and mobility (γ and preβ). We conclude that PL-rich particles, similarly to HDL, promote the release of surface material components from VLDL during LPL-mediated lipolysis and positively influence VLDL features which can facilitate VLDL metabolism. Such PC-L activity may impact on its antiatherogenic properties.
脂蛋白脂肪酶(LPL)介导的极低密度脂蛋白(VLDL)中的三酰甘油(TAG)水解伴随着含有磷脂(PL)、游离胆固醇(FC)以及载脂蛋白E(apoE)和载脂蛋白C(apoCII、apoCIII)的表面物质的释放。释放出的分子被高密度脂蛋白(HDL)摄取,同时还会生成新的具有HDL大小的含apoE颗粒。HDL颗粒数量的减少或其结构异常与VLDL残余物特征的不利变化相关。磷脂酰胆碱脂质体(PC-L)也可作为脂蛋白释放的表面物质成分的受体。因此,本研究的目的是评估脂质体对VLDL在LPL介导的脂解过程中组成变化的影响。从人血清中分离出的VLDL与LPL(LPL:VLDLTAG;24μg/ml:90mg/dl)和/或PC-L(VLDLPL:PC-LPL;重量比1:30)一起孵育。孵育(2小时,37℃)后,将VLDL与其他反应产物分离,并分析VLDL的脂质和载脂蛋白含量。通过二维非变性梯度凝胶电泳(2D-PAGGE)分离新生成的具有HDL大小的含apoE脂蛋白。在有或无LPL存在的情况下,VLDL与PC-L的反应显著影响VLDL的组成。VLDL中核心(TAG + 胆固醇酯)与表面(PL + FC)脂质的比例,在与PC-L反应时降低了1.8倍,与LPL反应时降低了1.2倍,与PC-L + LPL反应时降低了3倍。与PC-L和PC-L + LPL的反应分别使apoCs/apoE平均重量比降低了3.7倍和3.2倍。在PC-L影响下VLDL的组成变化伴随着VLDL脂解效率的提高以及生成大小(约9至约18.8nm)和迁移率(γ和前β)各异的含apoE的HDL大小颗粒。我们得出结论,富含PL的颗粒与HDL类似,在LPL介导的脂解过程中促进VLDL表面物质成分的释放,并对VLDL特征产生积极影响,这有助于VLDL代谢。这种PC-L活性可能会影响其抗动脉粥样硬化特性。