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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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002086 |
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| author | Maria Teresa La Chica Lhoëst Andrea Martínez Eduardo Garcia Jany Dandurand Anna Polishchuk Aleyda Benitez-Amaro Ana Cenarro Fernando Civeira Amable Bernabé David Vilades Joan Carles Escolà-Gil Valerie Samouillan Vicenta Llorente-Cortes |
| author_facet | Maria Teresa La Chica Lhoëst Andrea Martínez Eduardo Garcia Jany Dandurand Anna Polishchuk Aleyda Benitez-Amaro Ana Cenarro Fernando Civeira Amable Bernabé David Vilades Joan Carles Escolà-Gil Valerie Samouillan Vicenta Llorente-Cortes |
| author_sort | Maria Teresa La Chica Lhoëst |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-20fa92c95ad746e4bcc3d3e5dcf99634 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-20fa92c95ad746e4bcc3d3e5dcf996342025-01-30T05:12:36ZengElsevierJournal of Lipid Research0022-22752025-01-01661100703ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patientsMaria Teresa La Chica Lhoëst0Andrea Martínez1Eduardo Garcia2Jany Dandurand3Anna Polishchuk4Aleyda Benitez-Amaro5Ana Cenarro6Fernando Civeira7Amable Bernabé8David Vilades9Joan Carles Escolà-Gil10Valerie Samouillan11Vicenta Llorente-Cortes12Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, Spain; Biochemistry Department, Universitat Autònoma de Barcelona, Barcelona, SpainExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, SpainExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, Spain; Biochemistry Department, Universitat Autònoma de Barcelona, Barcelona, SpainCIRIMAT, Université de Toulouse Paul Sabatier, Equipe PHYPOL, Toulouse, FranceExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, SpainExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, SpainHospital 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, Madrid, SpainHospital 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, Madrid, SpainInstitut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, Bellaterra, SpainCIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, Madrid, Spain; Cardiac Imaging Unit, Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB SANT PAU, Barcelona, SpainCardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, Spain; Biochemistry Department, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainCIRIMAT, Université de Toulouse Paul Sabatier, Equipe PHYPOL, Toulouse, France; For correspondence: Vicenta Llorente-Cortes; Valerie SamouillanExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain; Cardiovascular Area, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Cardiovascular Area, Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques IIB Sant Pau, Barcelona, Spain; CIBER de Enfermedades Cardiovasculares CIBERCV, Institute of Health Carlos III, Madrid, Spain; For correspondence: Vicenta Llorente-Cortes; Valerie SamouillanPatients 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.http://www.sciencedirect.com/science/article/pii/S0022227524002086familiar hypercholesterolemiaLDL aggregationApoB100FTIRDSCsecondary structures |
| spellingShingle | Maria Teresa La Chica Lhoëst Andrea Martínez Eduardo Garcia Jany Dandurand Anna Polishchuk Aleyda Benitez-Amaro Ana Cenarro Fernando Civeira Amable Bernabé David Vilades Joan Carles Escolà-Gil Valerie Samouillan Vicenta Llorente-Cortes ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients Journal of Lipid Research familiar hypercholesterolemia LDL aggregation ApoB100 FTIR DSC secondary structures |
| title | 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_short | 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 |
| topic | familiar hypercholesterolemia LDL aggregation ApoB100 FTIR DSC secondary structures |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002086 |
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