Oxidative modification of a specific apolipoprotein B lysine residue confers altered receptor specificity on LDL

During inflammation, many cell types release reactive oxygen species (ROS) via the respiratory burst. These ROS are potent oxidants of LDL and its major protein, apolipoprotein B. Whilst native LDL is taken up by endothelial cells via a feedback controlled receptor-regulated process, oxidative modification of LDL renders it a ligand for many scavenger receptors. Scavenger receptors include CD-36, LOX-1 and the prototypic macrophage SR A I/II, all of which are variably expressed. Uncontrolled uptake of oxidised LDL is implicated in the pathogenesis of atherosclerosis. In addition, oxidised LDL increases CCR2 protein and mRNA expression on monocytes, and thus may contribute to monocyte retention and perpetuation in inflammatory, unstable atherosclerotic lesions. However, little data are available on the effects of specific minor modifications to apolipoprotein B. In order to identify the sequence specificity and nature of oxidative modifications which confer altered properties on LDL, we have investigated the effects of modified peptides (which correspond to the putative LDLR binding domain) on LDL uptake by HUVECs and U937 monocytes.