148867 20260217205544.0 doi 10.1016/j.jlr.2024.100703 sideral 142074 ART-2024-142074 eng La Chica Lhoëst, Maria Teresa ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients 2024 Access copy available to the general public Unrestricted 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, after exposure to sphingomyelinase, which breaks down sphingomyelin in the LDL phospholipid layer. Dynamic light scattering and transmission electron microscopy 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 showed that LDL from FH patients had higher transition temperatures, indicating a more ordered CE core. Fourier transform infrared 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 ApoB100 conformational structure as a new potential therapeutic targets within LDL to reduce cardiovascular risk in FH patients. info:eu-repo/grantAgreement/ES/FIS/PI21-01523 info:eu-repo/grantAgreement/ES/MINECO/RED2018-102799-T info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 4.1 2024 BIOCHEMISTRY & MOLECULAR BIOLOGY 104 / 320 = 0.325 2024 Q2 T1 1.66 2024 Biochemistry 2024 Q1 Endocrinology 2024 Q1 Cell Biology 2024 Q1 7.9 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Martínez, Andrea Garcia, Eduardo Dandurand, Jany Polishchuk, Anna Benitez-Amaro, Aleyda Cenarro, Ana Civeira, Fernando Universidad de Zaragoza (orcid)0000-0001-7043-0952 Bernabé, Amable Vilades, David Escolà-Gil, Joan Carles Samouillan, Valerie Llorente-Cortes, Vicenta 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 66, 1 (2024), 100703 [17 pp.] J. lipid res. Journal of Lipid Research 0022-2275 3949429 http://zaguan.unizar.es/record/148867/files/texto_completo.pdf Versión publicada 3108337 http://zaguan.unizar.es/record/148867/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:148867 articulos driver 2026-02-17-20:37:37 ARTICLE