Oxidation of lipoprotein(a) and low density lipoprotein containing density gradient ultracentrifugation fractions

Abstract

Increased plasma concentrations of lipoprotein(a) (Lp(a)) are associated with an increased risk for atherosclerotic cardiovascular disease. It is thought that the atherogenicity of Lp(a) is mediated both through its LDL-like properties and its plasminogen-like properties. In this study we have investigated the LDL-like atherogenic properties of Lp(a) by comparing the susceptibility to in vitro oxidation of Lp(a) and LDL isolated from the same subject. The subjects studied varied widely in plasma Lp(a) concentration (331-1829 mg/l) and Lp(a) phenotype (from B to S4). Lipoproteins are notoriously unstable in vitro, consequently differences in in vitro handling could influence oxidizability. Therefore, the isolation and handling of Lp(a) and LDL were performed in an identical fashion. Lp(a) and LDL containing fractions were obtained by density gradient ultracentrifugation. Separate fractions containing various amounts of Lp(a) and LDL, quantitated by measuring both Lp(a) and apo B-100, were subsequently oxidized on equimolar apo B-100 basis. Despite large differences in the Lp(a)/apo B-100 ratio of the various fractions (ranging from 5.3 +/- 1.7 to 0.2 +/- 0.1) they showed quite similar oxidation characteristics. The most dense Lp(a) containing fractions showed an aberrant susceptibility to oxidation. Subsequent gel filtration and reconstitution experiments showed that this was due to protein (i.e., albumin) contamination. Removal of excess protein revealed an oxidation pattern similar to that of LDL. It is concluded that the susceptibility of Lp(a) to lipid-peroxidation is similar to that of LDL when isolated simultaneously and in the same way from the same subject. Thus, lipid-peroxidation of Lp(a) is not influenced by the presence of its distinguishing apolipoprotein(a).