Differing α-Tocopherol Oxidative Lability and Ascorbic Acid Sparing Effects in Buoyant and Dense LDL

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Abstract
Abstract The enhanced oxidizability of smaller, more dense LDL is explained in part by a lower content of antioxidants, including ubiquinol-10 and α-tocopherol. In the present studies, we also observed greater rates of depletion of α-tocopherol (mole per mole LDL per minute) in dense ( d =1.040 to 1.054 g/mL) compared with buoyant ( d =1.026 to 1.032 g/mL) LDL in the presence of either Cu 2+ or the radical-generating agent 2,2′-azobis(2-amidinopropane)dihydrochloride. Differences were particularly pronounced at the lowest Cu 2+ concentration tested (0.25 μmol/L), with a fivefold greater rate in dense LDL. At higher concentrations (1.0 and 2.5 μmol/L Cu 2+ ), there was a greater dependence of depletion rate on initial amount of α-tocopherol, which was reduced in dense LDL, thus resulting in smaller subfraction-dependent differences in depletion rates. Inclusion of ascorbic acid (15 μmol/L), an aqueous antioxidant capable of recycling α-tocopherol by hydrogen donation, was found to extend the course of Cu 2+ -induced α-tocopherol depletion in both buoyant and dense LDL, but this effect was more pronounced in dense LDL (time to half-maximal α-tocopherol depletion was extended 15.6-fold and 21.2-fold in buoyant and dense LDL, respectively, at 2.5 μmol/L Cu 2+ ; P <.05). Thus, dense LDL exhibits more rapid α-tocopherol depletion and conjugated diene formation than buoyant LDL when oxidation is performed in the absence of ascorbic acid, but these differences are reversed in the presence of ascorbic acid. These results suggest that differences in oxidative behavior among LDL density subfractions may involve differences in antioxidant activity and thus that the efficacy of antioxidant regimens designed to inhibit LDL oxidation in vivo may vary in relation to interindividual variations in LDL particle distribution profiles.

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