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Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Centre for Biointerfaces (BRCB). Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, Cedex 9, France.ORCID iD: 0000-0003-3458-887X
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Centre for Biointerfaces (BRCB).ORCID iD: 0000-0002-7405-6125
Department of Pharmacy, Copenhagen University, Universitetsparken 2, 2100 Copenhagen, Denmark.
MAX IV Laboratory, Fotongatan 2, 225 92 Lund, Sweden.ORCID iD: 0000-0001-6547-5427
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2020 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1865, no 10, article id 158769Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2020. Vol. 1865, no 10, article id 158769
Keywords [en]
Cholesterol, Lipid removal, Lipoproteins, Neutron reflection, Saturated fats
National Category
Biochemistry Molecular Biology
Identifiers
URN: urn:nbn:se:mau:diva-18012DOI: 10.1016/j.bbalip.2020.158769ISI: 000563386500006PubMedID: 32712249Scopus ID: 2-s2.0-85088787543OAI: oai:DiVA.org:mau-18012DiVA, id: diva2:1458633
Available from: 2020-08-17 Created: 2020-08-17 Last updated: 2026-02-03Bibliographically approved
In thesis
1. Model Membranes and Their Interactions with Native and Artificial Lipoproteins
Open this publication in new window or tab >>Model Membranes and Their Interactions with Native and Artificial Lipoproteins
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atherosclerosis arises from build-up of plaque in the blood, can result in cardiovascular disease and is the largest killer in the west. Low- and high-density lipoproteins are involved in the disease development by depositing and removing lipids to and from artery walls. These processes are complex and not fully understood however, therefore determining the specific roles of the components involved is of fundamental importance in the treatment of the disease.

The work presented in this thesis investigates the production of recombinant tailor-deuterated cholesterol, the structure of cholesterol-containing model membranes and interactions of both native and reconstituted lipoproteins with model membranes. Deuteration is commonly used in neutron scattering for biological samples to provide highly important contrast and the complexity of the native lipoproteins leads to the use of more simple model systems where the compositions can be altered and investigated systematically.

A protocol was developed to produce matchout-deuterated cholesterol for use in neutron scattering studies, as cholesterol is a hugely important component in membranes. The verification of the matchpoint of cholesterol was determined by small-angle neutron scattering and the localisation of cholesterol in model membranes was determined through the use of neutron reflectometry. The interactions of the native and reconstituted lipoproteins with model membranes were also followed by neutron reflectometry, while the structural characterisation of the reconstituted lipoproteins was carried out by small-angle scattering.

Place, publisher, year, edition, pages
Malmö: Malmö universitet, 2020. p. 74
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2020:4
Keywords
Model Cell Membranes, Cholesterol, Lipoproteins, Apolipoprotein E, Lipid Exchange, Reconstituted HDL, Atherosclerosis, Deuteration, Neutron Reflectometry, Small-Angle Neutron Scattering
National Category
Physical Chemistry Biochemistry Molecular Biology
Identifiers
urn:nbn:se:mau:diva-36867 (URN)10.24834/isbn.9789178771325 (DOI)978-91-7877-131-8 (ISBN)978-91-7877-132-5 (ISBN)
Public defence
2020-11-25, Orkanen Hall D138, Nordenskiöldsgatan 10, Malmö, 13:00 (English)
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Supervisors
Available from: 2020-11-18 Created: 2020-11-18 Last updated: 2025-02-20Bibliographically approved

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Waldie, SarahSebastiani, FedericaMaric, SelmaLind, Tania KBengtsson, EvaCárdenas, Marité

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