The ApoE Mimetic Peptide, Ac-hE18A-NH2 Recycles in THP-1 Monocyte-Derived Macrophages

摘要

ApolipoproteinE (apoE) mimetic peptide Ac-hE18A-NH2 was designed to test the hypothesis that covalently linking the arginine rich putative receptor binding region from residues 141-150 of apoE (LRKLRKRLLR) to a class A amphipathic helical peptide 18A (DWLKAFYDKVAEKLKEAF) would produce a peptide with cholesterol lowering properties as well as anti-inflammatory properties. We have already shown the ability of this peptide to bind to apolipoprotein-B (apo-B) containing lipoproteins and enhance their clearance both in vivo and in vitro [l].We have also shown that injecting this peptide causes rapid clearance of plasma cholesterol in different dyslipidemic mouse models because of its ability to cause rapid uptake and degradation of apo-B containing lipoproteins [2]. Such an effect was not observed with Ac-18A-NH2 (2F). Injection of this peptide into Watanabe Heritable Hvperlinidemic Rabbits caused a dramatic reduction in plasma cholesterol levels and also reduced plasma lipid hydroperoxide levels [3]. The objective of this study was to determine if the addition of LRKLRKRLLR to 18A alters the cellular function of 2F.