Esterified lipid hydroperoxide-derived modification of protein: formation of a carboxyalkylamide-type lysine adduct in human atherosclerotic lesions

We have recently identified N-epsilon-azelayllysine (AZL) as a carboxyalkylamide-type novel lysine adduct in the reaction of linoleic acid hydroperoxides with the lysine derivative. To examine the formation of AZL in vivo, a novel monoclonal antibody (mAb19D5) specific to AZL moiety was prepared. The mAb19D5 scarcely recognized oxidized low-density lipoprotein (oxLDL), whereas the treatment of oxLDL with alkali or phospholipase A(2) significantly increased the immunoreactivity. Similarly, the immunopositive materials were detected in alkali- or phospholipase A(2)-treated sections from human atherosclerotic aorta but not in untreated sections. These results suggest that esterified lipid hydroperoxide-derived modification of protein may serve as one mechanism for the oxidative modification of LDL and subsequent formation of atherosclerotic lesions in vivo. (C) 2003 Published by Elsevier Inc.