Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol

Sarah Waldie,Federica Sebastiani,Kathryn Browning,Selma Maric,Tania K Lind,Nageshwar Yepuri,Tamim A Darwish,Martine Moulin,Gernot Strohmeier,Harald Pichler,Maximilian W.A Skoda,Armando Maestro,Michael Haertlein,V Trevor Forsyth,Eva Bengtsson,Martin Malmsten,Marité Cárdenas

doi:10.1016/j.bbalip.2020.158769

Abstract

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.

Highlights

Atherosclerosis is the largest killer in the west and accounted for an estimated 17.9 million deaths in 2016 [1]
Neutron reflection can differentiate between deuterium-la belled and hydrogen-rich lipids as shown schematically in Fig. 1, al lowing quantification of both lipid exchange and lipid removal from the model membranes by lipoproteins
We present data of lipid exchange between pooled li poprotein fractions extracted from human blood and model membranes composed of either saturated or unsaturated phospholipids, in the presence or absence of cholesterol

Summary

Introduction

Atherosclerosis is the largest killer in the west and accounted for an estimated 17.9 million deaths in 2016 [1] It is a leading cause of cardiovascular disease (CVD), which in turn originates from the buildup of plaque on artery walls. This plaque build-up arises from the de position of lipoproteins, which are subsequently oxidised, in turn initiating an active inflammatory process and taken up by macro phages. The macrophages develop into foam cells filled with lipids and cholesterol, over time forming a hard plaque. If this plaque ruptures, blood will be exposed to thrombogenic material, which can result in a heart attack or stroke [2]. De spite this, the initial interaction of lipoprotein particles with the membrane wall remains poorly understood, notably in relation to lipid exchange from lipoprotein to the cell membrane and vice versa

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Conclusion