Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

Dainius Jakubauskas; Martin Jansen; Jeppe Lyngsø; Yuanji Cheng; Jan Skov Pedersen; Marité Cárdenas

doi:10.1016/j.nano.2020.102318

Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

Dainius Jakubauskas, Martin Jansen, Jeppe Lyngsø, Yuanji Cheng, Jan Skov Pedersen, Marité Cárdenas^*

^*Corresponding author for this work

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Abstract

Atherosclerosis is the main killer in the west and therefore a major health challenge today. Total serum cholesterol and lipoprotein concentrations, used as clinical markers, fail to predict the majority of cases, especially between the risk scale extremes, due to the high complexity in lipoprotein structure and composition. In particular, low-density lipoprotein (LDL) plays a key role in atherosclerosis development, with LDL size being a parameter considered for determining the risk for cardiovascular diseases. Determining LDL size and structural parameters is challenging to address experimentally under physiological-like conditions. This article describes the biochemistry and ultrastructure of normolipidemic and hypertriglyceridemic LDL fractions and subfractions using small-angle X-ray scattering. Our results conclude that LDL particles of hypertriglyceridemic compared to healthy individuals 1) have lower LDL core melting temperature, 2) have lower cholesteryl ester ordering in their core, 3) are smaller, rounder and more spherical below melting temperature, and 4) their protein-containing shell is thinner above melting temperature.

Original language	English
Article number	102318
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	31
Number of pages	13
ISSN	1549-9634
DOIs	https://doi.org/10.1016/j.nano.2020.102318
Publication status	Published - Jan 2021

Keywords

Cardiovascular diseases
Hypertriglyceridemia
LDL structure
LDL subfractionation
Low-density lipoprotein
Small-angle X-ray scattering
SAXS

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10.1016/j.nano.2020.102318Licence: CC BY

1-s2.0-S1549963420301726-mainFinal published version, 3 MBLicence: CC BY

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Jakubauskas, D., Jansen, M., Lyngsø, J., Cheng, Y., Pedersen, J. S., & Cárdenas, M. (2021). Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels. Nanomedicine: Nanotechnology, Biology, and Medicine, 31, Article 102318. https://doi.org/10.1016/j.nano.2020.102318

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title = "Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels",

abstract = "Atherosclerosis is the main killer in the west and therefore a major health challenge today. Total serum cholesterol and lipoprotein concentrations, used as clinical markers, fail to predict the majority of cases, especially between the risk scale extremes, due to the high complexity in lipoprotein structure and composition. In particular, low-density lipoprotein (LDL) plays a key role in atherosclerosis development, with LDL size being a parameter considered for determining the risk for cardiovascular diseases. Determining LDL size and structural parameters is challenging to address experimentally under physiological-like conditions. This article describes the biochemistry and ultrastructure of normolipidemic and hypertriglyceridemic LDL fractions and subfractions using small-angle X-ray scattering. Our results conclude that LDL particles of hypertriglyceridemic compared to healthy individuals 1) have lower LDL core melting temperature, 2) have lower cholesteryl ester ordering in their core, 3) are smaller, rounder and more spherical below melting temperature, and 4) their protein-containing shell is thinner above melting temperature.",

keywords = "Cardiovascular diseases, Hypertriglyceridemia, LDL structure, LDL subfractionation, Low-density lipoprotein, Small-angle X-ray scattering, SAXS",

author = "Dainius Jakubauskas and Martin Jansen and Jeppe Lyngs{\o} and Yuanji Cheng and Pedersen, {Jan Skov} and Marit{\'e} C{\'a}rdenas",

year = "2021",

month = jan,

doi = "10.1016/j.nano.2020.102318",

language = "English",

volume = "31",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

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Jakubauskas, D, Jansen, M, Lyngsø, J, Cheng, Y, Pedersen, JS & Cárdenas, M 2021, 'Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 31, 102318. https://doi.org/10.1016/j.nano.2020.102318

Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels. / Jakubauskas, Dainius; Jansen, Martin; Lyngsø, Jeppe et al.
In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 31, 102318, 01.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions

T2 - A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

AU - Jakubauskas, Dainius

AU - Jansen, Martin

AU - Lyngsø, Jeppe

AU - Cheng, Yuanji

AU - Pedersen, Jan Skov

AU - Cárdenas, Marité

PY - 2021/1

Y1 - 2021/1

N2 - Atherosclerosis is the main killer in the west and therefore a major health challenge today. Total serum cholesterol and lipoprotein concentrations, used as clinical markers, fail to predict the majority of cases, especially between the risk scale extremes, due to the high complexity in lipoprotein structure and composition. In particular, low-density lipoprotein (LDL) plays a key role in atherosclerosis development, with LDL size being a parameter considered for determining the risk for cardiovascular diseases. Determining LDL size and structural parameters is challenging to address experimentally under physiological-like conditions. This article describes the biochemistry and ultrastructure of normolipidemic and hypertriglyceridemic LDL fractions and subfractions using small-angle X-ray scattering. Our results conclude that LDL particles of hypertriglyceridemic compared to healthy individuals 1) have lower LDL core melting temperature, 2) have lower cholesteryl ester ordering in their core, 3) are smaller, rounder and more spherical below melting temperature, and 4) their protein-containing shell is thinner above melting temperature.

AB - Atherosclerosis is the main killer in the west and therefore a major health challenge today. Total serum cholesterol and lipoprotein concentrations, used as clinical markers, fail to predict the majority of cases, especially between the risk scale extremes, due to the high complexity in lipoprotein structure and composition. In particular, low-density lipoprotein (LDL) plays a key role in atherosclerosis development, with LDL size being a parameter considered for determining the risk for cardiovascular diseases. Determining LDL size and structural parameters is challenging to address experimentally under physiological-like conditions. This article describes the biochemistry and ultrastructure of normolipidemic and hypertriglyceridemic LDL fractions and subfractions using small-angle X-ray scattering. Our results conclude that LDL particles of hypertriglyceridemic compared to healthy individuals 1) have lower LDL core melting temperature, 2) have lower cholesteryl ester ordering in their core, 3) are smaller, rounder and more spherical below melting temperature, and 4) their protein-containing shell is thinner above melting temperature.

KW - Cardiovascular diseases

KW - Hypertriglyceridemia

KW - LDL structure

KW - LDL subfractionation

KW - Low-density lipoprotein

KW - Small-angle X-ray scattering

KW - SAXS

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DO - 10.1016/j.nano.2020.102318

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SN - 1549-9634

VL - 31

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

M1 - 102318

ER -

Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

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Keywords

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