A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma.

Research paper by Ayelet A Gonen, Soo-Ho SH Choi, Phuong P Miu, Colin C Agatisa-Boyle, Daniel D Acks, Angela M AM Taylor, Coleen A CA McNamara, Sotirios S Tsimikas, Joseph L JL Witztum, Yury I YI Miller

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: Journal of lipid research


Atherosclerosis is associated with increased lipid peroxidation, leading to generation of multiple oxidation-specific epitopes (OSEs), contributing to the pathogenesis of atherosclerosis and its clinical manifestation. Oxidized cholesteryl esters (OxCE) is a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCE as a candidate biomarker, we generated a novel mouse monoclonal antibody (mAb) specific to an OxCE modification of proteins. The mAb AG23 (IgG1) was raised in C57BL6 mice immunized with OxCE-modified KLH, and hybridomas were screened against OxCE-modified BSA. This method ensures mAb specificity to the OxCE modification, independent of a carrier protein. AG23 specifically stained human carotid artery atherosclerotic lesions. An ELISA method, with AG23 as a capture and either anti-apoAI or anti-apoB-100 as the detection antibodies, was developed to assay apoAI and apoB-100 lipoproteins that have one or more OxCE epitopes. OxCE-apoA or OxCE-apoB did not correlate with the well-established oxidized phospholipid OxPL-apoB biomarker. In a cohort of subjects treated with atorvastatin, OxCE-apoA was significantly lower than in the placebo group, independent of the apoAI levels. These results suggest the potential diagnostic utility of a new biomarker assay to measure OxCE-modified lipoproteins in patients with cardiovascular disease. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.