Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins

PURPOSE: Elevated plasma concentrations of low-density liproteins (LDL) inc rease risk for coronary heart disease. However, lipoprotein profiles rich i n small, dense LDL particles confer greater risk than those that mainly con sist of large, buoyant LDL. This may be due, in part, to the greater oxidat ive susceptibility of small, dense LDL. In the current studies, we tested w hether differences in the oxidative behavior of buoyant and dense LDL. aris e from differences in their immediate metabolic precursors, intermediate-de nsity lipoproteins. SUBJECTS AND METHODS: We compared the properties of intermediate-density li poproteins and buoyant and dense LDL subfractions in 9 subjects with the la rge, buoyant LDL phenotype vet sus 6 with the small, dense LDL phenotype. O xidative susceptibility was evaluated based on conjugated diene formation a nd parinaric acid oxidation induced by copper. Antioxidants (ubiquinol- 10 and a-tocopherol) were measured by highperformance liquid chromatography. RESULTS: Oxidative susceptibility was increased and antioxidant concentrati ons were decreased with increasing lipoprotein density (intermediate interm ediate-density lipoproteins to buoyant LDL to dense LDL). Intermediate-dens ity lipoproteins from subjects with the small, dense LDL phenotype had a gr eater oxidative susceptibility (by the parinaric acid test) and lower antio xidant concentrations than corresponding particles from subjects with the l arge, buoyant LDL phenotype. CONCLUSIONS: Differences in oxidative susceptibility be tween large, buoyan t and small, dense LDL particles are apparent in their lipoprotein precurso rs. These results suggest that lipoprotein oxidative susceptibility may be metabolically programmed and that intermediate-density lipoproteins ma): co n tribute to the increased risk associated with the small, dense LDL phenot ype. (C) 2001 by Excerpta Medica, Inc.