Aggregated electronegative low density lipoprotein in human plasma shows a high tendency toward phospholipolysis and particle fusion
Por:
Bancells C., Villegas S., Blanco F.J., Benítez S., Gállego I., Beloki L., Pérez-Cuellar M., Ordóñez-Llanos J., Sánchez-Quesada J.L.
Publicada:
1 ene 2010
Resumen:
Aggregation and fusion of lipoproteins trigger subendothelial retention of cholesterol, promoting atherosclerosis. The tendency of a lipoprotein to form fused particles is considered to be related to its atherogenic potential. We aimed to isolate and characterize aggregated and nonaggregated subfractions of LDL from human plasma, paying special attention to particle fusion mechanisms. Aggregated LDL was almost exclusively found in electronegative LDL (LDL(-)), a minor modified LDL subfraction, but not in native LDL (LDL(+)). The main difference between aggregated (agLDL(-)) and nonaggregated LDL(-) (nagLDL(-)) was a 6-fold increased phospholipase C-like activity in agLDL(-). agLDL(-) promoted the aggregation of LDL(+) and nagLDL(-). Lipoprotein fusion induced by a-chymotrypsin proteolysis was monitored by NMR and visualized by transmission electron microscopy. Particle fusion kinetics was much faster in agLDL(-) than in nagLDL(-) or LDL(+). NMR and chromatographic analysis revealed a rapid and massive phospholipid degradation in agLDL(-) but not in nagLDL(-) or LDL(+). Choline-containing phospholipids were extensively degraded, and ceramide, diacylglycerol, monoacylglycerol, and phosphorylcholine were the main products generated, suggesting the involvement of phospholipase C-like activity. The properties of agLDL(-) suggest that this subfraction plays a major role in atherogenesis by triggering lipoprotein fusion and cholesterol accumulation in the arterial wall. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Filiaciones:
Bancells C.:
Departament de Bioquímica I Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
Villegas S.:
Departament de Bioquímica I Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Blanco F.J.:
IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain
CIC BioGUNE, Parque Tecnológico de Bizkaia, Edificio 800, 48160 Derio, Spain
Benítez S.:
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
Gállego I.:
Departament de Bioquímica I Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Beloki L.:
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
Pérez-Cuellar M.:
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
Ordóñez-Llanos J.:
Departament de Bioquímica I Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
Sánchez-Quesada J.L.:
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain
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