OXIDATION OF LIPOPROTEIN(A) AND LOW-DENSITY-LIPOPROTEIN CONTAINING DENSITY GRADIENT ULTRACENTRIFUGATION FRACTIONS

Increased plasma concentrations of lipoprotein(a) (:Lp(a)) are associa ted with an increased risk for atherosclerotic cardiovascular disease. It is thought that the atherogenicity of Lp(a) is mediated both throu gh its LDL-like properties and its plasminogen-like properties. In thi s 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 widel y in plasma Lp(a) concentration (331-1829 mg/l) and Lp(a) phenotype (f rom B to S4). Lipoproteins are notoriously unstable in vitro, conseque ntly differences in in vitro handling could influence oxidizability. T herefore, the isolation and handling of Lp(a) and LDL were performed i n an identical fashion. Lp(a) and LDL containing fractions were obtain ed by density gradient ultracentrifugation. Separate fractions contain ing 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 b asis. Despite large differences in the Lp(a)/apo B-100 ratio of the va rious fractions (ranging from 5.3 +/- 1.7 to 0.2 +/- 0.1) they showed quire similar oxidation characteristics. The most dense Lp(a) containi ng fractions showed an aberrant susceptibility to oxidation. Subsequen t gel filtration and reconstitution experiments showed that this was d ue 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 t he presence of its distinguishing apolipoprotein(a).