000148867 001__ 148867
000148867 005__ 20260217205544.0
000148867 0247_ $$2doi$$a10.1016/j.jlr.2024.100703
000148867 0248_ $$2sideral$$a142074
000148867 037__ $$aART-2024-142074
000148867 041__ $$aeng
000148867 100__ $$aLa Chica Lhoëst, Maria Teresa
000148867 245__ $$aApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients
000148867 260__ $$c2024
000148867 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148867 5203_ $$aPatients 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.
000148867 536__ $$9info:eu-repo/grantAgreement/ES/FIS/PI21-01523$$9info:eu-repo/grantAgreement/ES/MINECO/RED2018-102799-T
000148867 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000148867 590__ $$a4.1$$b2024
000148867 592__ $$a1.66$$b2024
000148867 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b104 / 320 = 0.325$$c2024$$dQ2$$eT1
000148867 593__ $$aBiochemistry$$c2024$$dQ1
000148867 593__ $$aEndocrinology$$c2024$$dQ1
000148867 593__ $$aCell Biology$$c2024$$dQ1
000148867 594__ $$a7.9$$b2024
000148867 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000148867 700__ $$aMartínez, Andrea
000148867 700__ $$aGarcia, Eduardo
000148867 700__ $$aDandurand, Jany
000148867 700__ $$aPolishchuk, Anna
000148867 700__ $$aBenitez-Amaro, Aleyda
000148867 700__ $$aCenarro, Ana
000148867 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, Fernando$$uUniversidad de Zaragoza
000148867 700__ $$aBernabé, Amable
000148867 700__ $$aVilades, David
000148867 700__ $$aEscolà-Gil, Joan Carles
000148867 700__ $$aSamouillan, Valerie
000148867 700__ $$aLlorente-Cortes, Vicenta
000148867 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000148867 773__ $$g66, 1 (2024), 100703 [17 pp.]$$pJ. lipid res.$$tJournal of Lipid Research$$x0022-2275
000148867 8564_ $$s3949429$$uhttps://zaguan.unizar.es/record/148867/files/texto_completo.pdf$$yVersión publicada
000148867 8564_ $$s3108337$$uhttps://zaguan.unizar.es/record/148867/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000148867 909CO $$ooai:zaguan.unizar.es:148867$$particulos$$pdriver
000148867 951__ $$a2026-02-17-20:37:37
000148867 980__ $$aARTICLE