Development of antibody against epitope of lipoprotein(a) modified by oxidation - Evaluation of new enzyme-linked immunosorbent assay for oxidized lipoprotein(a)

Background-Recently, the biological effects of oxidized lipoprotein(a) [Lp( a)] have been reported to be more potent than Lp(a), the arteriosclerosis-r elevant lipoprotein, Thus, investigations with oxidized Lp(a) are expected to provide viewpoints different from the conventional ones based on Lp(a). Methods and Results-An anti-1p(a) monoclonal antibody (161E2) was produced against synthetic peptide antigen (Arg-Asn-Pro-Asp-Val-Ala-Pro). This epito pe was characterized as having various properties because its external expo sure was induced as a result of oxidative modification, Using 161E2 antibod y, we developed a new enzyme-linked immunosorbent assay to measure Lp(a) mo dified by oxidative stress. The present data demonstrated that oxidized Lp( a) that contains the epitope of 161E2 antibody was present in the serum of humans. Therefore, we used this new enzyme-linked immunosorbent assay to ev aluate the role of oxidized Lp(a) in patients with hypertension, which indu ces oxidative stress, Interestingly, hypertensive patients with complicatio ns showed a significantly higher level of oxidized Lp(a) in serum than did normotensive subjects (P<0.01), whereas there was no significant difference in native Lp(a) between normotensive and hypertensive subjects, Importantl y, positive immunostaining with 161E2 monoclonal antibody was found in the human arteriosclerotic tissue. Conclusions-We developed a new antibody against an epitope in Lp(a) as a re sult of oxidation treatment but not in native Lp(a). The present data demon strated in vivo the presence of oxidized Lp(a) in the atherosclerotic tissu e and its elevation in hypertensive patients. The presence of oxidized Lp(a ) may be important in understanding the role of Lp(a) in cardiovascular dis ease.