Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol

Yetukuri, LaxmanVTT Technical Research Centre of Finland, Espoo, Finland (author)

Funding agencies:European Union FP7-KBBE-222639 Finnish Heart Foundation Sigrid Juselius Foundation Helsinki University Central Hospital Research Foundation
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.

Söderlund, SanniDivision of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland (author)
Koivuniemi, ArtturiDepartment of Physics, Tampere University of Technology, Tampere, Finland (author)
Seppänen-Laakso, TuulikkiVTT Technical Research Centre of Finland, Espoo, Finland (author)
Niemelä, Perttu S.VTT Technical Research Centre of Finland, Espoo, Finland (author)
Hyvönen, MarjaDepartment of Physics, University of Oulu, Oulu, Finland (author)
Taskinen, Marja-RiittaDivision of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland (author)
Vattulainen, IlpoDepartment of Physics, Tampere University of Technology, Tampere, Finland; Department of Physics, Aalto University School of Science and Engineering, Espoo, Finland; MEMPHYS – Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark (author)
Jauhiainen, MattiNational Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland (author)
Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland; Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland(Swepub:oru)moc (author)
VTT Technical Research Centre of Finland, Espoo, FinlandDivision of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland (creator_code:org_t)

In:Journal of Lipid Research: American Society for Biochemistry and Molecular Biology51:8, s. 2341-23510022-22751539-7262

By the author/editor: Yetukuri, Laxman; Söderlund, Sanni; Koivuniemi, Artt ...; Seppänen-Laakso, ...; Niemelä, Perttu ...; Hyvönen, Marja; show more...; Taskinen, Marja- ...; Vattulainen, Ilp ...; Jauhiainen, Matt ...; Oresic, Matej, 1 ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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