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@ARTICLE{Correa:638194,
author = {Correa, Yubexi and Nzekwe, Favour and Wodaje, Tigist and
Brinck, Jonas and Jansen, Martin and Blanchet, Clement and
Pedersen, Jan Skov and Del Giudice, Rita and Cárdenas,
Marité},
title = {{S}tructural, functional and biochemical characterisation
of apolipoprotein(a)-containing low-density lipoproteins},
journal = {Journal of colloid and interface science},
volume = {701},
issn = {0021-9797},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PUBDB-2025-04012},
pages = {138760 -},
year = {2025},
abstract = {Atherosclerosis is the leading cause of cardiovascular
diseases and remains a global health challenge. Low-density
lipoproteins are crucial in atherogenesis, with plasma
levels as significant independent predictors of the
condition. Lipoprotein(a), Lp(a), is an LDL variant
considered a stand-alone atherosclerosis predictor. Although
structurally similar in composition to LDL, Lp(a) contains
an additional protein, apolipoprotein(a), covalently linked
to apolipoprotein-B100 via a disulfide bond. This
distinguishing protein is believed to confer Lp(a) its
distinctive properties, including marked heterogeneity.
While many studies have structurally characterised LDL
particles, Lp(a) remains understudied. In this study, we
isolated LDL particles from serum of normolipidemic, healthy
individuals with either low or high Lp(a) levels. Our study
provides biochemical, structural and functional
characterisation of low and high Lp(a)-total LDL fractions.
Fourier transform infrared spectroscopy (FTIR) revealed that
high Lp(a) LDL exhibited a reduced ability to remove lipids
from model membranes compared to low Lp(a) LDL. However,
this functional difference could not be sufficiently
associated with structural differences in total LDL
fractions, as determined by small-angle X-ray scattering
(SAXS), except for a significant difference in the
particles' core-to-shell scattering mass (SM) ratio. Western
blot analysis further revealed a higher abundance of Lp(a)
in a small-dense subfraction, LDL6, leading us to
hypothesise that structural differences might be more
evident in these subfractions than in total fractions.
Supporting this hypothesis, SAXS measurements on LDL6
subfractions from two subjects, with low and high Lp(a),
revealed an increased protein shell thickness in high Lp(a)
LDL6, a feature not directly observed in total fractions.
Our data thus suggests a key role of LDL6 in LDL
dysfunction.},
cin = {EMBL-User / EMBL},
ddc = {540},
cid = {I:(DE-H253)EMBL-User-20120814 / I:(DE-H253)EMBL-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P12-20150101},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.jcis.2025.138760},
url = {https://bib-pubdb1.desy.de/record/638194},
}