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

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 15; no. 11; pp. 2025 - 2031
• Main Authors: Tribble, Diane L, Thiel, Patrick M, van den Berg, Jeroen J.M, Krauss, Ronald M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.11.1995; Hagerstown, MD Lippincott
• Subjects: Ascorbic Acid - pharmacology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Centrifugation, Density Gradient; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - metabolism; Medical sciences; Molecular Weight; Oxidants - pharmacology; Oxidation-Reduction; Vitamin E - pharmacology; Vascular disease; Human; Lipoprotein LDL; Ascorbic acid; Atherosclerosis; Cardiovascular disease; Exploration; α-Tocopherol; Antioxidant
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.15.11.2025

The enhanced oxidizability of smaller, more dense LDL is explained in part by a lower content of antioxidants, including ubiquinol-10 and alpha-tocopherol. In the present studies, we also observed greater rates of depletion of alpha-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 Copper+ or the radical-generating agent 2,2'-azobis(2-amidinopropane)dihydrochloride. Differences were particularly pronounced at the lowest Copper+ concentration tested (0.25 micro mol/L), with a fivefold greater rate in dense LDL. At higher concentrations (1.0 and 2.5 micro mol/L Copper+), there was a greater dependence of depletion rate on initial amount of alpha-tocopherol, which was reduced in dense LDL, thus resulting in smaller subfraction-dependent differences in depletion rates. Inclusion of ascorbic acid (15 micro mol/L), an aqueous antioxidant capable of recycling alpha-tocopherol by hydrogen donation, was found to extend the course of Copper+ -induced alpha-tocopherol depletion in both buoyant and dense LDL, but this effect was more pronounced in dense LDL (time to half-maximal alpha-tocopherol depletion was extended 15.6-fold and 21.2-fold in buoyant and dense LDL, respectively, at 2.5 micro mol/L Copper+; P < .05). Thus, dense LDL exhibits more rapid alpha-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. (Arterioscler Thromb Vasc Biol. 1995;15:2025-2031.).