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

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...

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Autores: La Chica Lhoëst, María Teresa|||0000-0002-9070-5973, Martínez, Andrea, García Rodríguez, Jesús Eduardo|||0000-0002-7758-6789, Dandurand, Jany, Polishchuk, Anna, Benitez Amaro, Aleyda|||0000-0002-1106-3125, Cenarro, Ana, Civeira, Fernando|||0000-0001-7043-0952, Bernabé, Amable, Viladés Medel, David|||0000-0002-3638-9703, Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Samouillan, Valerie|||0000-0003-0571-3985, Llorente-Cortés, Vicenta|||0000-0002-0067-7201
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:306627
Acceso en línea:https://ddd.uab.cat/record/306627
https://dx.doi.org/urn:doi:10.1016/j.jlr.2024.100703
Access Level:acceso abierto
Palabra clave:Familiar hypercholesterolemia
LDL aggregation
ApoB100
FTIR
DSC
Secondary structures
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spelling ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patientsLa Chica Lhoëst, María Teresa|||0000-0002-9070-5973Martínez, AndreaGarcía Rodríguez, Jesús Eduardo|||0000-0002-7758-6789Dandurand, JanyPolishchuk, AnnaBenitez Amaro, Aleyda|||0000-0002-1106-3125Cenarro, AnaCiveira, Fernando|||0000-0001-7043-0952Bernabé, AmableViladés Medel, David|||0000-0002-3638-9703Escolà-Gil, Joan Carles|||0000-0001-9021-2485Samouillan, Valerie|||0000-0003-0571-3985Llorente-Cortés, Vicenta|||0000-0002-0067-7201Familiar hypercholesterolemiaLDL aggregationApoB100FTIRDSCSecondary structuresPatients 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. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/306627https://dx.doi.org/urn:doi:10.1016/j.jlr.2024.100703reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/01523Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 21/01173Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/11/00276Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-00834open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3066272026-06-06T12:50:31Z
dc.title.none.fl_str_mv ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
title ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
spellingShingle ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
La Chica Lhoëst, María Teresa|||0000-0002-9070-5973
Familiar hypercholesterolemia
LDL aggregation
ApoB100
FTIR
DSC
Secondary structures
title_short ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
title_full ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
title_fullStr ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
title_full_unstemmed ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
title_sort ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
dc.creator.none.fl_str_mv La Chica Lhoëst, María Teresa|||0000-0002-9070-5973
Martínez, Andrea
García Rodríguez, Jesús Eduardo|||0000-0002-7758-6789
Dandurand, Jany
Polishchuk, Anna
Benitez Amaro, Aleyda|||0000-0002-1106-3125
Cenarro, Ana
Civeira, Fernando|||0000-0001-7043-0952
Bernabé, Amable
Viladés Medel, David|||0000-0002-3638-9703
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Samouillan, Valerie|||0000-0003-0571-3985
Llorente-Cortés, Vicenta|||0000-0002-0067-7201
author La Chica Lhoëst, María Teresa|||0000-0002-9070-5973
author_facet La Chica Lhoëst, María Teresa|||0000-0002-9070-5973
Martínez, Andrea
García Rodríguez, Jesús Eduardo|||0000-0002-7758-6789
Dandurand, Jany
Polishchuk, Anna
Benitez Amaro, Aleyda|||0000-0002-1106-3125
Cenarro, Ana
Civeira, Fernando|||0000-0001-7043-0952
Bernabé, Amable
Viladés Medel, David|||0000-0002-3638-9703
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Samouillan, Valerie|||0000-0003-0571-3985
Llorente-Cortés, Vicenta|||0000-0002-0067-7201
author_role author
author2 Martínez, Andrea
García Rodríguez, Jesús Eduardo|||0000-0002-7758-6789
Dandurand, Jany
Polishchuk, Anna
Benitez Amaro, Aleyda|||0000-0002-1106-3125
Cenarro, Ana
Civeira, Fernando|||0000-0001-7043-0952
Bernabé, Amable
Viladés Medel, David|||0000-0002-3638-9703
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Samouillan, Valerie|||0000-0003-0571-3985
Llorente-Cortés, Vicenta|||0000-0002-0067-7201
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Familiar hypercholesterolemia
LDL aggregation
ApoB100
FTIR
DSC
Secondary structures
topic Familiar hypercholesterolemia
LDL aggregation
ApoB100
FTIR
DSC
Secondary structures
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/306627
https://dx.doi.org/urn:doi:10.1016/j.jlr.2024.100703
url https://ddd.uab.cat/record/306627
https://dx.doi.org/urn:doi:10.1016/j.jlr.2024.100703
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/01523
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 21/01173
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/11/00276
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-00834
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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