ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients

La Chica Lhoëst, Maria Teresa ; Martínez, Andrea ; Garcia, Eduardo ; Dandurand, Jany ; Polishchuk, Anna ; Benitez-Amaro, Aleyda ; Cenarro, Ana ; Civeira, Fernando (Universidad de Zaragoza) ; Bernabé, Amable ; Vilades, David ; Escolà-Gil, Joan Carles ; Samouillan, Valerie ; Llorente-Cortes, Vicenta

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.jlr.2024.100703

Año: 2024

Publicado en: Journal of Lipid Research 66, 1 (2024), 100703 [17 pp.]
ISSN: 0022-2275

Factor impacto JCR: 4.1 (2024)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 104 / 320 = 0.325 (2024) - Q2 - T1

Factor impacto CITESCORE: 7.9 - Biochemistry (Q1) - Endocrinology (Q1) - Cell Biology (Q2)

Factor impacto SCIMAGO: 1.66 - Biochemistry (Q1) - Endocrinology (Q1) - Cell Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS/PI21-01523
Financiación: info:eu-repo/grantAgreement/ES/MINECO/RED2018-102799-T

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)