Department of Pharmacy, Uppsala University, Uppsala, Sweden; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Department of Biomedical Sciences and Biofilms - Research Centre for Biointerfaces, Malmö University, Malmö, Sweden.
Colloids Surf B Biointerfaces. 2018 Aug 1;168:117-125. doi: 10.1016/j.colsurfb.2018.01.043. Epub 2018 Jan 31.
Lipoproteins play a key role in the onset and development of atherosclerosis, the formation of lipid plaques at blood vessel walls. The plaque formation, as well as subsequent calcification, involves not only endothelial cells but also connective tissue, and is closely related to a wide range of cardiovascular syndromes, that together constitute the number one cause of death in the Western World. High (HDL) and low (LDL) density lipoproteins are of particular interest in relation to atherosclerosis, due to their protective and harmful effects, respectively. In an effort to elucidate the molecular mechanisms underlying this, and to identify factors determining lipid deposition and exchange at lipid membranes, we here employ neutron reflection (NR) and quartz crystal microbalance with dissipation (QCM-D) to study the effect of membrane charge on lipoprotein deposition and lipid exchange. Dimyristoylphosphatidylcholine (DMPC) bilayers containing varying amounts of negatively charged dimyristoylphosphatidylserine (DMPS) were used to vary membrane charge. It was found that the amount of hydrogenous material deposited from either HDL or LDL to the bilayer depends only weakly on membrane charge density. In contrast, increasing membrane charge resulted in an increase in the amount of lipids removed from the supported lipid bilayer, an effect particularly pronounced for LDL. The latter effects are in line with previously reported observations on atherosclerotic plaque prone regions of long-term hyperlipidaemia and type 2 diabetic patients, and may also provide some molecular clues into the relation between oxidative stress and atherosclerosis.
脂蛋白在动脉粥样硬化的发生和发展中起着关键作用，它是血管壁脂质斑块的形成。斑块的形成以及随后的钙化不仅涉及内皮细胞，还涉及结缔组织，并且与广泛的心血管综合征密切相关，这些综合征共同构成了西方世界头号死亡原因。高密度脂蛋白（HDL）和低密度脂蛋白（LDL）在与动脉粥样硬化有关，因为它们分别具有保护和有害的作用。为了阐明这一现象的分子机制，并确定决定脂质在脂质膜上沉积和交换的因素，我们在这里采用中子反射（NR）和石英晶体微天平（QCM-D）来研究膜电荷对脂蛋白沉积和脂质交换的影响。含有不同量带负电荷的二肉豆蔻酰磷脂酰丝氨酸（DMPS）的二肉豆蔻酰磷脂酰胆碱（DMPC）双层用于改变膜电荷。结果发现，无论是从 HDL 还是 LDL 沉积到双层的氢物质的量仅弱依赖于膜电荷密度。相比之下，增加膜电荷会导致从支撑脂质双层中去除的脂质量增加，对于 LDL 尤其明显。后一种效应与先前报道的长期高脂血症和 2 型糖尿病患者动脉粥样硬化斑块易发生区域的观察结果一致，并且可能还为氧化应激与动脉粥样硬化之间的关系提供了一些分子线索。
