Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins.
OBJECTIVE
Elevated plasma concentrations of low-density lipoproteins (LDL) increase risk for coronary heart disease. However, lipoprotein profiles rich in small, dense LDL particles confer greater risk than those that mainly consist of large, buoyant LDL. This may be due, in part, to the greater oxidative susceptibility of small, dense LDL. In the current studies, we tested whether differences in the oxidative behavior of buoyant and dense LDL arise from differences in their immediate metabolic precursors, intermediate-density lipoproteins.


METHODS
We compared the properties of intermediate-density lipoproteins and buoyant and dense LDL subfractions in 9 subjects with the large, buoyant LDL phenotype versus 6 with the small, dense LDL phenotype. Oxidative susceptibility was evaluated based on conjugated diene formation and parinaric acid oxidation induced by copper. Antioxidants (ubiquinol-10 and alpha-tocopherol) were measured by high-performance liquid chromatography.


RESULTS
Oxidative susceptibility was increased and antioxidant concentrations were decreased with increasing lipoprotein density (intermediate intermediate-density lipoproteins to buoyant LDL to dense LDL). Intermediate-density lipoproteins from subjects with the small, dense LDL phenotype had a greater oxidative susceptibility (by the parinaric acid test) and lower antioxidant concentrations than corresponding particles from subjects with the large, buoyant LDL phenotype.


CONCLUSIONS
Differences in oxidative susceptibility between large, buoyant and small, dense LDL particles are apparent in their lipoprotein precursors. These results suggest that lipoprotein oxidative susceptibility may be metabolically programmed and that intermediate-density lipoproteins may contribute to the increased risk associated with the small, dense LDL phenotype.
Tribble
D L
DL
Department of Molecular and Nuclear Medicine, Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.
Rizzo
M
M
Chait
A
A
Lewis
D M
DM
Blanche
P J
PJ
Krauss
R M
RM
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction; D010641:Phenotype; D012016:Reference Values
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; C013641:parinaric acid