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J Lipid Res. 2019 Feb;60(2):436-445. doi: 10.1194/jlr.D090852. Epub 2018 Dec 18.

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

Author information

1
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
2
Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, VA 22908.
3
Department of Medicine, University of California, San Diego, La Jolla, CA 92093 yumiller@ucsd.edu.

Abstract

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 (OxCEs) are a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCEs as a candidate biomarker, we generated a novel mouse monoclonal Ab (mAb) specific to an OxCE modification of proteins. The mAb AG23 (IgG1) was raised in C57BL6 mice immunized with OxCE-modified keyhole limpet hemocyanin, 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 Abs, 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-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 CVD.

KEYWORDS:

apolipoprotein AI; apolipoprotein B-100; biomarker; oxidation-specific epitope

PMID:
30563909
PMCID:
PMC6358287
[Available on 2020-02-01]
DOI:
10.1194/jlr.D090852

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