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

• Published in: Journal of lipid research Vol. 51; no. 8; pp. 2341 - 2351
• Main Authors: Yetukuri, Laxman, Söderlund, Sanni, Koivuniemi, Artturi, Seppänen-Laakso, Tuulikki, Niemelä, Perttu S., Hyvönen, Marja, Taskinen, Marja-Riitta, Vattulainen, Ilpo, Jauhiainen, Matti, Orešič, Matej
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2010; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Cholesterol, HDL - metabolism; Chromatography, High Pressure Liquid; Cohort Studies; Computational Biology; Female; high density lipoprotein; Humans; lipid metabolism; lipidomics; Lipoproteins, HDL - chemistry; Lipoproteins, HDL - metabolism; Male; Mass Spectrometry; Middle Aged; molecular dynamics; Molecular Dynamics Simulation; Protein Conformation; Triglycerides - metabolism; high density lipoprotein; molecular dynamics; lipidomics; lipid metabolism
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.M006494

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.