Document Detail


Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol.
MedLine Citation:
PMID:  20431113     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Laxman Yetukuri; Sanni Söderlund; Artturi Koivuniemi; Tuulikki Seppänen-Laakso; Perttu S Niemelä; Marja Hyvönen; Marja-Riitta Taskinen; Ilpo Vattulainen; Matti Jauhiainen; Matej Oresic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-29
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-15     Completed Date:  2010-10-20     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2341-51     Citation Subset:  IM    
Affiliation:
VTT Technical Research Centre of Finland, Espoo, Finland.
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MeSH Terms
Descriptor/Qualifier:
Cholesterol, HDL / metabolism*
Chromatography, High Pressure Liquid
Cohort Studies
Computational Biology
Female
Humans
Lipoproteins, HDL / chemistry*,  metabolism*
Male
Mass Spectrometry
Middle Aged
Molecular Dynamics Simulation
Protein Conformation
Triglycerides / metabolism
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Lipoproteins, HDL; 0/Triglycerides
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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