ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
La Chica Lhoëst, Maria Teresa (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Martínez, Andrea (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
García Rodríguez, Jesús Eduardo (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Dandurand, Jany (Université de Toulouse Paul Sabatier)
Polishchuk, Anna (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Benitez Amaro, Aleyda (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Cenarro, Ana (Hospital Universitario Miguel Servet (Saragossa))
Civeira, Fernando (Hospital Universitario Miguel Servet (Saragossa))
Bernabé, Amable (Institut de Ciència de Materials de Barcelona)
Vilades, David (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Escolà-Gil, Joan Carles (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Samouillan, Valerie (Université de Toulouse Paul Sabatier)
Llorente-Cortés, Vicenta (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))

Data:	2024
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI21/01523 Instituto de Salud Carlos III 21/01173 Ministerio de Economía y Competitividad CB16/11/00276 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00834
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Familiar hypercholesterolemia ; LDL aggregation ; ApoB100 ; FTIR ; DSC ; Secondary structures
Publicat a:	Journal of Lipid Research, Vol. 66 (november 2024) , ISSN 1539-7262

DOI: 10.1016/j.jlr.2024.100703
PMID: 39557294

17 p, 3.8 MB

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