Abstract 454: Cationic Peptides Neutralize Ox-LDL and Acetyl LDL Negative Charge and Prevent Their Uptake by Macrophages

Abstract

Background Apoprotein (Apo A1) and apoprotein E mimetic peptides are known to reduce atherosclerosis. Antioxidant, anti-inflammatory, and hypolipidemic properties have been suggested to contribute to the anti-atherosclerotic effects. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins and inhibit their uptake by macrophages. Methods 5F-mimetic peptide of apoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide were commercially synthesized. The number of positively charged amino acid residues (K+R) and negatively charged residues (D+E) were 4/4, 7/4, 6/2 respectively. Their abilities to reduce lipid peroxides (LOOH), inhibit the oxidation low density lipoprotein (LDL) and high density lipoprotein (HDL), interact with modified lipoproteins, and to inhibit macrophage uptake of modified LDL were measured. Results Cationic peptides decomposed the peroxide content of 13-HPODE and inhibited the oxidation of LDL and HDL by copper in a lysine dependent manner. Incubation of Ox-LDL and Ac-LDL with the peptides resulted in charge neutralization as noted by agarose gel electrophoresis. Pre-incubation of the peptides with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining. Conclusions Based on these studies, we postulate that cationic peptides may have properties that may affect a) events that are unrelated to lipid lowering, b) may play additional role in immune competent cells, including macrophages, and c) may interact with other biologically important anionic molecules, including lipids and proteins. These results also suggest there may be other cationic proteins that may influence the atherogenic processes.