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Journal of Lipid Research, Vol. 43, 699-705, May 2002
Copyright © 2002 by Lipid Research, Inc.

Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects

José Luis Sánchez-Quesada^*, Sonia Benítez^*, Carles Otal^*, Miquel Franco, Francisco Blanco-Vaca^* and Jordi Ordóñez-Llanos^1,*,

^* Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Servei de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Spain

¹ To whom correspondence should be addressed at Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/Antoni María Claret 167, 08025 Barcelona, Spain. e-mail: 2038{at}hsp.santpau.es

The density distribution of electronegative LDL [LDL(-)], a cytotoxic and inflammatory fraction of LDL present in plasma, was studied in 10 normolipemic (NL), 6 FH, and 11 hypertriglyceridemic (HTG) subjects. Six LDL subclasses of increased density (LDL1 to LDL6) were isolated by density-gradient ultracentrifugation (DGU). NL and FH subjects showed prevalence of light LDL, whereas HTG subjects showed prevalence of dense LDL. LDL(-) proportion was determined from total LDL or LDL-density subclasses by anion-exchange chromatography. LDL from FH patients had increased LDL(-) (35.1 ± 9.9%) compared with LDL from NL and HTG subjects (9.4 ± 2.3% and 12.3 ± 4.3%, respectively). Most LDL(-) was contained in dense subclasses in NL (LDL4–6, 67.7 ± 3.1%) whereas most of LDL(-) from FH patients were contained in light LDL subclasses (LDL1–3) (86.2 ± 1.6%). In these subjects, simvastatin therapy decreased LDL(-) to 28.2 ± 6.7% and 21.2 ± 5.6% at 3 and 6 months of treatment, respectively, due mainly to decreases in light LDL subclasses. In HTG subjects, half LDL(-) was contained in dense LDL subclasses (LDL4–6, 46.1 ± 2.0%). Non-denaturing acrylamide gradient gel electrophoresis concurred with DGU data, as LDL(-) from NL showed a single band of lower size than non-electronegative LDL [LDL(+)], whereas LDL(-) from FH and HTG presented bands of greater size than its respective LDL(+). These results reveal the existence of light and dense LDL(-), indicate that hyperlipemia could promote the formation of light LDL(-) and suggest that LDL(-) could have different origins.—Sánchez-Quesada, J. L., S. Benítez, C. Otal, M. Franco, F. Blanco-Vaca, and J. Ordóñez-Llanos. Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects. J. Lipid Res. 2002. 43: 699–705.

Abbreviations: DGU, density gradient ultracentrifugation; FPLC, fast protein liquid chromatography; GGE, gradient gel electrophoresis; HTG, hypertrigliceridemic; LDL(-), electronegative LDL; NL, normolipemic

Supplementary key words modified LDL • LDL density subclasses • hyperlipemia

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