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

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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

Fingerprint

HDL Cholesterol
Spatial distribution
LDL Cholesterol
Lipids
Chemical analysis
Lipoproteins
Triglycerides
Lysophosphatidylcholines
Sphingomyelins
Apolipoprotein A-I
Molecular Dynamics Simulation
Lipid Metabolism
Particle Size
Metabolism
Computer Simulation
Molecular dynamics
Cardiovascular Diseases
Particle size
Computer simulation
Proteins

Keywords

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

Cite this

Yetukuri, Laxman ; Söderlund, Sanni ; Koivuniemi, Artturi ; Seppänen-Laakso, Tuulikki ; Niemelä, Perttu ; Hyvönen, Marja ; Taskinen, Marja-Riitta ; Vattulainen, Ilpo ; Jauhiainen, Matti ; Oresic, Matej. / Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol. In: Journal of Lipid Research. 2010 ; Vol. 51, No. 8. pp. 2341-2351.
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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.",
keywords = "High-density lipoprotein, lipidomics, lipid metabolism, molecular dynamics",
author = "Laxman Yetukuri and Sanni S{\"o}derlund and Artturi Koivuniemi and Tuulikki Sepp{\"a}nen-Laakso and Perttu Niemel{\"a} and Marja Hyv{\"o}nen and Marja-Riitta Taskinen and Ilpo Vattulainen and Matti Jauhiainen and Matej Oresic",
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doi = "10.1194/jlr.M006494",
language = "English",
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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, vol. 51, no. 8, pp. 2341-2351. https://doi.org/10.1194/jlr.M006494

Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol. / Yetukuri, Laxman; Söderlund, Sanni; Koivuniemi, Artturi; Seppänen-Laakso, Tuulikki; Niemelä, Perttu; Hyvönen, Marja; Taskinen, Marja-Riitta; Vattulainen, Ilpo; Jauhiainen, Matti; Oresic, Matej (Corresponding Author).

In: Journal of Lipid Research, Vol. 51, No. 8, 2010, p. 2341-2351.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol

AU - Yetukuri, Laxman

AU - Söderlund, Sanni

AU - Koivuniemi, Artturi

AU - Seppänen-Laakso, Tuulikki

AU - Niemelä, Perttu

AU - Hyvönen, Marja

AU - Taskinen, Marja-Riitta

AU - Vattulainen, Ilpo

AU - Jauhiainen, Matti

AU - Oresic, Matej

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - High-density lipoprotein

KW - lipidomics

KW - lipid metabolism

KW - molecular dynamics

U2 - 10.1194/jlr.M006494

DO - 10.1194/jlr.M006494

M3 - Article

VL - 51

SP - 2341

EP - 2351

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 8

ER -