Inhibitory Effects of LRP1-Based Immunotherapy on Cardiac Extracellular Matrix Biophysical Alterations Induced by Hypercholesterolemia
Por:
Samouillan, V, Garcia, E, Benitez-Amaro, A, Lhoest, MTLC, Dandurand, J, Dato, VA, Guerra, JM, Escola-Gil, JC, Chiabrando, G, Enrich, C, Llorente-Cortes, V
Publicada:
11 may 2023
Ahead of Print:
1 abr 2023
Resumen:
The accumulation of lipids in cardiomyocytes contributes to cardiac dysfunction. The specific blockage of cardiomyocyte cholesteryl ester (CE) loading by antibodies (Abs) against the P3 sequence (Gly1127-Cys1140) of the LRP1 receptor improves cardiac insulin sensitivity. The impact of anti-P3 Abs on biophysical alterations was analyzed. Both IrP (without Abs) and P3immunized rabbits (with Abs) were randomized into groups fed either HFD or a standard chow diet. Cardiac lipids, proteins, and carbohydrates were characterized by Fourier transform infrared spectroscopy in the attenuated total reflectance mode. The hydric organization and physical structure were determined by differential scanning calorimetry. HFD increased the levels of esterified lipids, collagen, and alpha-helical structures and upregulated fibrosis, bound water, and ECM plasticization in the heart. The inhibitory effect of anti-P3 Abs on cardiac CE accumulation was sufficient to reduce the collagen-filled extracellular space, the level of fibrosis, and the amount of bound water but did not counteract ECM plasticization in the heart of hypercholesterolemic rabbits.
Filiaciones:
Samouillan, V:
Univ Paul Sabatier, Univ Toulouse, CIRIMAT, F-31062 Toulouse, France
Garcia, E:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St PAU, Barcelona 08041, Spain
Inst Biomed Res Barcelona, IIBB Spanish Natl Res Council CSIC, Barcelona 08036, Spain
Benitez-Amaro, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St PAU, Barcelona 08041, Spain
Inst Biomed Res Barcelona, IIBB Spanish Natl Res Council CSIC, Barcelona 08036, Spain
Lhoest, MTLC:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St PAU, Barcelona 08041, Spain
Inst Biomed Res Barcelona, IIBB Spanish Natl Res Council CSIC, Barcelona 08036, Spain
Dandurand, J:
Univ Paul Sabatier, Univ Toulouse, CIRIMAT, F-31062 Toulouse, France
Dato, VA:
Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, X5000HUA, Cordoba, Argentina
Consejo Nacl Invest Cient & Tecn, Ctr Invest Bioquim Clin & Inmunol CIBICI, RA-2290 Buenos Aires, Argentina
Guerra, JM:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau IIB SANTPAU, Dept Cardiol, Barcelona 08025, Spain
Escola-Gil, JC:
Biomed Res Inst St Pau IIB St Pau, Metab Basis Cardiovasc Risk, Barcelona 08041, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBERD, Madrid 28029, Spain
Chiabrando, G:
Inst Univ Ciencias Biomed Cordoba IUCBC, Ctr Invest Med Translac Severo R Amuch stegui CIME, GV Inst Invest Med Mercedes & Martin Ferreyra, INIMEC CONICET UNC, X5016KEJ, Cordoba, Argentina
Enrich, C:
Univ Barcelona, Dept Biomed, Unitat Biol Cellular, Fac Med & Ciencies Salut, Barcelona 08036, Spain
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Ctr Recerca Biome CELLEX, Barcelona 08036, Spain
Llorente-Cortes, V:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St PAU, Barcelona 08041, Spain
Inst Biomed Res Barcelona, IIBB Spanish Natl Res Council CSIC, Barcelona 08036, Spain
Inst Hlth Carlos III, CIBERCV, Madrid 28029, Spain
Green Published, hybrid, All Open Access, Hybrid Gold, Green
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