Department of Biomedical Science and Biofilms - Research Center for Biointerfaces, Malmö University, 20506 Malmö, Sweden; Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, Cedex 9, France.
Department of Biomedical Science and Biofilms - Research Center for Biointerfaces, Malmö University, 20506 Malmö, Sweden.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Oct;1865(10):158769. doi: 10.1016/j.bbalip.2020.158769. Epub 2020 Jul 23.
Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease. In order to elucidate the impact of phospholipid tail saturation and the presence of cholesterol in cell membranes on these processes, neutron reflection was employed in the present investigation to follow lipid exchange with both HDL and LDL against model membranes. Mirroring clinical risk factors for the development of atherosclerosis, lower exchange was observed in the presence of cholesterol, as well as for an unsaturated phospholipid, compared to faster exchange when using a fully saturated phospholipid. These results highlight the importance of membrane composition on the interaction with lipoproteins, chiefly the saturation level of the lipids and presence of cholesterol, and provide novel insight into factors of importance for build-up and reversibility of atherosclerotic plaque. In addition, the correlation between the results and well-established clinical risk factors suggests that the approach taken can be employed also for understanding a broader set of risk factors including, e.g., effects of triglycerides and oxidative stress, as well as local effects of drugs on atherosclerotic plaque formation.
脂蛋白在动脉粥样硬化的发展中起着核心作用。高密度脂蛋白(HDL)和低密度脂蛋白(LDL)分别被称为“好”和“坏”胆固醇,它们将脂质从血液中清除并/或沉积到动脉壁中。因此,深入了解脂蛋白与细胞膜之间的脂质交换过程对于理解心血管疾病的发生和发展具有重要意义。为了阐明细胞膜中磷脂尾部饱和度和胆固醇的存在对这些过程的影响,本研究采用中子反射技术研究了 HDL 和 LDL 与模型膜之间的脂质交换。与动脉粥样硬化发展的临床风险因素相吻合的是,胆固醇的存在以及不饱和磷脂的存在会导致脂质交换减慢,而使用完全饱和的磷脂时脂质交换则更快。这些结果突出了膜组成对与脂蛋白相互作用的重要性,主要是脂质的饱和度和胆固醇的存在,并为了解动脉粥样硬化斑块形成和逆转的重要因素提供了新的见解。此外,结果与既定的临床风险因素之间的相关性表明,所采用的方法还可以用于理解更广泛的风险因素,例如甘油三酯和氧化应激的影响,以及药物对动脉粥样硬化斑块形成的局部影响。