Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol.
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.
Yetukuri
Laxman
L
VTT Technical Research Centre of Finland, Espoo, Finland.
Söderlund
Sanni
S
Koivuniemi
Artturi
A
Seppänen-Laakso
Tuulikki
T
Niemelä
Perttu S
PS
Hyvönen
Marja
M
Taskinen
Marja-Riitta
MR
Vattulainen
Ilpo
I
Jauhiainen
Matti
M
Oresic
Matej
M
D008076:Cholesterol, HDL / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D014280:Triglycerides / Q000378:metabolism
D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D014280:Triglycerides