Aggregated electronegative low density lipoprotein in human plasma shows a high tendency toward phospholipolysis and particle fusion.
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 α-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.
Bancells
Cristina
C
Departament de Bioquímica, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
Villegas
Sandra
S
Blanco
Francisco J
FJ
Benítez
Sonia
S
Gállego
Isaac
I
Beloki
Lorea
L
Pérez-Cuellar
Montserrat
M
Ordóñez-Llanos
Jordi
J
Sánchez-Quesada
José Luis
JL
D050197:Atherosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D002918:Chymotrypsin / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D008077:Lipoproteins, LDL; D010743:Phospholipids; D002784:Cholesterol; D010738:Type C Phospholipases; D002918:Chymotrypsin; C117608:alpha-chymotrypsin