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

Laxman Yetukuri, Sanni Söderlund, Artturi Koivuniemi, Tuulikki Seppänen-Laakso, Perttu Niemelä, Marja Hyvönen, Marja-Riitta Taskinen, Ilpo Vattulainen, Matti Jauhiainen, Matej Oresic (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

79 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)2341-2351
Number of pages11
JournalJournal of Lipid Research
Volume51
Issue number8
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Keywords

  • High-density lipoprotein
  • lipidomics
  • lipid metabolism
  • molecular dynamics

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    Yetukuri, L., Söderlund, S., Koivuniemi, A., Seppänen-Laakso, T., Niemelä, P., Hyvönen, M., Taskinen, M-R., Vattulainen, I., Jauhiainen, M., & Oresic, M. (2010). Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol. Journal of Lipid Research, 51(8), 2341-2351. https://doi.org/10.1194/jlr.M006494