ubiquinol and Arteriosclerosis

The oxidation of low density lipoprotein (LDL) is now commonly regarded as an important early event in atherogenesis. As such there is considerable interest in the ability of antioxidant supplementation to attenuate LDL oxidation and hence atherosclerosis. A majority of studies on LDL antioxidation have focused on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, circulating LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q). Recent studies have shown that in intact, isolated LDL, alpha-TOH can act as either an anti- or prooxidant for the lipoprotein's lipids. This article reviews the molecular action of alpha-TOH in LDL undergoing radical-initiated oxidation, and how the presence of CoQ10H2 suppresses the pro-oxidant or complements the antioxidant activity of the vitamin. We also comment on the plasma and intimal levels of alpha-TOH and CoQ10H2 in patients suffering from coronary artery disease and discuss the potential implications of these results for atherogenesis.

Topics: Antioxidants; Arteriosclerosis; Coronary Artery Disease; Diet; Humans; Lipid Peroxidation; Lipoproteins, LDL; Models, Biological; Oxidation-Reduction; Peroxides; Ubiquinone; Vitamin E

The conjugated polyene fatty acid parinaric acid (PnA) undergoes a stoichiometric loss in fluorescence upon oxidation and can be used to directly monitor peroxidative stress within lipid environments. We evaluated the course of potentially atherogenic oxidative changes in low density lipoproteins (LDL) by monitoring the oxidation of PnA following its incorporation into buoyant (p = 1.026-1.032 g/ml) and dense (p = 1.040-1.054 g/ml) LDL subfractions. Copper-induced oxidation of LDL-associated PnA exhibited an initial lag phase followed by an increased rate of loss until depletion. Increased PnA oxidation occurred immediately after the antioxidants ubiquinol-10 and alpha-tocopherol were consumed but before there were marked elevations in conjugated dienes. Despite differences in sensitivity to early oxidation events, PnA oxidation and conjugated diene lag times were correlated (r = 0.582; P = 0.03), and both indicated a greater susceptibility of dense than buoyant LDL in accordance with previous reports. The greater susceptibility of PnA in dense LDL was attributed to reduced levels of ubiquinol-10 and alpha-tocopherol, which were approximately 50% lower than in buoyant LDL (mol of antioxidant/mol of LDL) and together accounted for 80% of the variation in PnA oxidation lag times. These results suggest that PnA is a useful probe of LDL oxidative susceptibility and may be superior to conjugated dienes for monitoring the initial stages of LDL lipid peroxidation. Differences in oxidative susceptibility among LDL density subfractions are detected by the PnA assay and are due in large part to differences in their antioxidant content.

Topics: Adult; Antioxidants; Arteriosclerosis; Fatty Acids, Unsaturated; Female; Fluorescent Dyes; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Oxidation-Reduction; Ubiquinone; Vitamin E