ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
Por:
Lhoëst, MTL, Martínez, A, Garcia, E, Dandurand, J, Polishchuk, A, Benitez-Amaro, A, Cenarro, A, Civeira, F, Bernabé, A, Vilades, D, Escolà-Gil, JC, Samouillan, V, Llorente-Cortes, V
Publicada:
1 ene 2025
Ahead of Print:
1 dic 2024
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 alpha-helices (1658 cm- 1 ) and more stable alpha-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 alpha-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.
Filiaciones:
Lhoëst, MTL:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Univ Autonoma Barcelona, Biochem Dept, Barcelona, Spain
Martínez, A:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Garcia, E:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Univ Autonoma Barcelona, Biochem Dept, Barcelona, Spain
Dandurand, J:
Univ Toulouse Paul Sabatier, Equipe PHYPOL, CIRIMAT, Toulouse, France
Polishchuk, A:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Benitez-Amaro, A:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Cenarro, A:
Univ Zaragoza, Hosp Univ Miguel Servet, IIS Aragon, Inst Aragones Ciencias Salud, Zaragoza, Spain
Inst Hlth Carlos III, CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Civeira, F:
Univ Zaragoza, Hosp Univ Miguel Servet, IIS Aragon, Inst Aragones Ciencias Salud, Zaragoza, Spain
Inst Hlth Carlos III, CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Bernabé, A:
CSIC, Inst Ciencia Mat Barcelona ICMAB, Campus UAB, Bellaterra, Spain
Vilades, D:
IIB ST PAU, Hosp Santa Creu i St Pau, Dept Cardiol, Cardiac Imaging Unit, Barcelona, Spain
Escolà-Gil, JC:
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Univ Autonoma Barcelona, Biochem Dept, Barcelona, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBERD, Madrid, Spain
Samouillan, V:
Univ Toulouse Paul Sabatier, Equipe PHYPOL, CIRIMAT, Toulouse, France
Llorente-Cortes, V:
CSIC, Inst Biomed Res Barcelona IIBB, Expt Pathol Dept, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Cardiovasc Area, Barcelona, Spain
Inst Invest Biomed IIB St Pau, Inst Recerca Hosp St Creu i St Pau, Cardiovasc Area, Barcelona, Spain
Inst Hlth Carlos III, CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Green Submitted, Green Accepted, gold
|