High Correlation Between Lp(a) Levels and the Presence of an Oxidation Specific Epitope on LDL in Human Plasma

C.Bergmark°, S. Hörkkö, K. Kuroe, JL Witztum

Specialized Center of Research in Molecular Medicine and Atherosclerosis, Univ of California, San Diego, La Jolla, CA, USA

°at present Department of Vascular Surgery, St. Görans Hospital, Stockholm, Sweden

We have cloned a murine autoantibody E06 which recognizes OxLDL and specifically recognizes oxidized phospholipids such as POVPC
(1-palmitoyl-2-(5-oxovaleroyl)-3-sn-phosphorylcholine). We developed a sandwich assay to measure the content of the E06 epitope on human LDL utilizing a monoclonal antibody to apoB to capture LDL from plasma and biotinylated E06 to detect the content of the OxPL epitope present on the captured LDL. When performing this test on a population of patients with premature peripheral vascular disease we surprisingly found a high correlation between Lp(a) levels and E06 levels (r=0.84 p
<0.0000). This was true in both the patients (r=0.90 p< 0.0000) and control populations (r=0.78 p< 0.0000). We have subsequently confirmed this strong association in three separate population studies. On Western blots Lp(a) does not immunostain with E06, suggesting that the antibody is not binding to intrinsic epitopes of (a). In summary, these data suggest that elevated Lp(a) levels are associated with an increased content of oxidized phospholipid epitopes on plasma LDL. It will be of interest to determine if this relates to the increased risk associated with high Lp(a) levels.