ApoB100 Remodeling and Stiffened Cholesteryl Ester Core Raise LDL Aggregation in Familial Hypercholesterolemia Patients.

Autor:	La Chica Lhoëst MT; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain., Martínez A; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain., Garcia E; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain., Dandurand J; CIRIMAT, Université de Toulouse Paul Sabatier, Equipe PHYPOL, 31062 Toulouse, France., Polishchuk A; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain., Benitez-Amaro A; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain., Cenarro A; Hospital Universitario Miguel Servet, IIS Aragón, Instituto Aragonés de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain; CIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain., Civeira F; Hospital Universitario Miguel Servet, IIS Aragón, Instituto Aragonés de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain; CIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain., Bernabé A; Institut de Ciència de Materials de Barcelona (ICMAB-CSIC). Campus UAB. E-08193, Bellaterra, Spain., Vilades D; Cardiac Imaging Unit, Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB SANT PAU, Barcelona, Spain; CIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain., Escola-Gil JC; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain., Samouillan V; CIRIMAT, Université de Toulouse Paul Sabatier, Equipe PHYPOL, 31062 Toulouse, France. Electronic address: valerie.samouillan@univ-tlse3.fr., Llorente CV; Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, 08041 Barcelona, Spain; CIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain. Electronic address: Vicenta.llorente@iibb.csic.es.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Nov 16, pp. 100703. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1016/j.jlr.2024.100703
Abstrakt:	Patients with familial hypercholesterolemia (FH) exhibit a significant residual cardiovascular risk. A new cardiovascular risk factor is the susceptibility of individual LDL particles to aggregation. This study examined LDL aggregation and its relationship with LDL lipid composition and biophysical properties in patients with FH compared to controls. LDL aggregation was measured as the change in particle size, assessed by dynamic light scattering (DLS), after exposure to sphingomyelinase (SMase), which breaks down sphingomyelin in the LDL phospholipid layer. DLS and transmission electron microscopy (TEM) showed that LDL in FH patients exhibited smaller size and greater susceptibility to aggregation. Biochemical analyses revealed a higher cholesteryl ester (CE)/ApoB100 ratio in LDL from FH patients. Differential Scanning Calorimetry (DSC) showed that LDL from FH patients had higher transition temperatures, indicating a more ordered CE core. Fourier-transform infrared (FTIR) spectroscopy revealed fewer flexible α-helices (1658 cm⁻ 1 ) and more stable α-helices (1651 cm⁻ 1 ) in ApoB100 of LDL from FH patients. These structural changes correlated with higher CE content and increased LDL aggregation. In conclusion, a more ordered CE core in smaller LDL particles, combined with a higher proportion of stable α-helices in ApoB100, promotes LDL aggregation in FH patients. These findings suggest new potential therapeutic targets within LDL to reduce cardiovascular risk in FH patients. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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