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Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol
VTT Technical Research Centre of Finland, Espoo, Finland.
Division of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland.
Department of Physics, Tampere University of Technology, Tampere, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
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2010 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 51, no 8, p. 2341-2351Article in journal (Refereed) Published
Abstract [en]

A low level of high density lipoprotein cholesterol (HDL-C) is a powerful risk factor for cardiovascular disease. However, despite the reported key role of apolipo-proteins, specifically, apoA-I, in HDL metabolism, lipid molecular composition of HDL particles in subjects with high and low HDL-C levels is currently unknown. Here lipidomics was used to study HDL derived from well-characterized high and low HDL-C subjects. Low HDL-C subjects had elevated triacylglycerols and diminished lysophosphatidylcholines and sphingomyelins. Using information about the lipid composition of HDL particles in these two groups, we reconstituted HDL particles in silico by performing large-scale molecular dynamics simulations. In addition to confirming the measured change in particle size, we found that the changes in lipid composition also induced specific spatial distributions of lipids within the HDL particles, including a higher amount of triacylglycerols at the surface of HDL particles in low HDL-C subjects. Our findings have important implications for understanding HDL metabolism and function. For the first time we demonstrate the power of combining molecular profiling of lipoproteins with dynamic modeling of lipoprotein structure.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2010. Vol. 51, no 8, p. 2341-2351
National Category
Medical and Health Sciences Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-63627DOI: 10.1194/jlr.M006494ISI: 000279896800030PubMedID: 20431113Scopus ID: 2-s2.0-77956815968OAI: oai:DiVA.org:oru-63627DiVA, id: diva2:1169193
Note

Funding agencies:

European Union FP7-KBBE-222639 

Finnish Heart Foundation  

Sigrid Juselius Foundation  

Helsinki University Central Hospital Research Foundation 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-05-02Bibliographically approved

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Oresic, Matej

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