Given the suggested patho-physiological significance of oxLDL, there has been a significant increase in the research of the pathogenic role of circulating oxLDL, giving new insights and questions in regards to the role of oxLDL in cardiovascular disease. Previously, indirect methods were used to assess LDL oxidation, mainly by measurement of susceptibility of LDL to oxidation and measurement of auto-antibodies to oxLDL. The introduction of specific monoclonal antibodies, which recognize different distinct oxidation epitopes has enabled the development of specific and sensitive immunoassays to measure the levels of circulating oxLDL.
Evidence on circulating oxLDL and its clinical significance to the diagnosis and prognosis of cardiovascular disease has grown substantially over the past years. Three different monoclonal antibodies that bind various epitopes of oxLDL have been described in detail. All three are murine monoclonal antibodies (DLH3, E06 and 4E6) and assays based on these antibodies have been used in various investigations. The monoclonal antibody 4E6 is directed against a conformational epitope in the ApoB-100 moiety of the LDL particle, generated as a consequence of substitution of at least 60 lysine residues of ApoB-100 with aldehydes. This number of substituted lysines also corresponds to the minimal number required for scavenger-mediated uptake of oxLDL. The specificity of the antibody 4E6 is different from the specificities of DLH3 and E06, which are reported to be directed against epitopes of oxidized phosphatidylcholine respectively to the phosphocholine head group, of oxidized but not native phospholipids.