Journal Article

PUBDB-2025-04012

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural, functional and biochemical characterisation of apolipoprotein(a)-containing low-density lipoproteins

Correa, Y. ; Nzekwe, F. ; Wodaje, T. ; Brinck, J. ; Jansen, M. ; Blanchet, C. ; Pedersen, J. S. ; Del Giudice, R. ; Cárdenas, M. (Corresponding author)Extern*

2025
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jcis.2025.138760

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.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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