How Different Constituents of Low Density Lipoprotein Determine its Oxidizability by Copper: A Correlational Approach

Abstract

Although low density lipoprotein (LDL) susceptibility to oxidation is expected to be primarily related to its composition, the individual contributions of different constituents to its oxidizability remain unclear. The present study was undertaken to elucidate how different constituents of isolated LDL determine its susceptibility to oxidation induced by Cu2+ under conditions close to those of the well-known Cu2+-oxidation assay (H. Esterbauer, G. Striegl, H. Puhl and M. Rotheneder (1989) Free Radical Research Communications, 6, 67–75). We characterized antioxidant, fatty acid and total lipid composition of human LDL from healthy donors (n = 22) and compared each with LDL oxidizability by Cu2+. LDL oxidizability was evaluated as oxidizability of antioxidant-containing LDL (rate of lipid peroxidation measured before total consumption of a-tocopherol, the major LDL antioxidant), oxidizability of antioxidant-depleted LDL (maximal rate of lipid peroxidation and maximal production of conjugated dienes within the propagation, antioxidant-depleted phase of oxidation) and overall LDL resistance to oxidation (duration of the lag-phase before the onset of the propagation phase). We found that the oxidizability of antioxidant-containing LDL correlated negatively with LDL content of ubiquinol-10 and free cholesterol, and positively with that of n-3 polyunsaturated fatty acids (PUFAs). LDL n-3 PUFAs, ubiquinol-10 and free cholesterol were the most important determinants of the oxidizability of antioxidant-containing LDL, contributing to about 35%, 25% and 25% of its total variability, respectively. Oxidizability of antioxidant-depleted LDL was largely determined by LDL PUFA content. The overall LDL resistance to oxidation correlated weakly with LDL chemical composition. α-Tocopherol was found to be only a minor contributor to the oxidizability of isolated LDL under oxidative conditions used (7.5 or 14 mol Cu 2+/mol LDL), It appears that the oxidizability of antioxidant-containing LDL represents a parameter highly sensitive to changing LDL composition, whereas the overall LDL resistance to oxidation combines contributions from different LDL constituents more uniformly, being weaker sensitive to individual factors. It is suggested that PUFAs, ubiquinol-10 and free cholesterol are the most important determinants of LDL oxidizability by Cu2+.