An apolipoprotein E synthetic peptide targets to lipoproteins in plasma and mediates both cellular lipoprotein interactions in vitro and acute clearance of cholesterol-rich lipoproteins in vivo

The Journal of Clinical Investigation
I R Nikoulin, L K Curtiss

Abstract

Apolipoprotein (apo) E mediates lipoprotein binding to cellular lipoprotein receptors. Previously we reported that a synthetic peptide representing a linear dimeric repeat of amino acids 141-155 binds cellular LDL receptors. To prepare an apoE peptide that bound to both cholesterol-rich lipoproteins and lipoprotein receptors, an NH2-terminal acetylated apoE dimer peptide was synthesized. This acetylated peptide preferentially associated with lipoproteins in plasma, whereas nonacylated peptides were poor lipid binders. Acetylated peptide/LDL complexes (molar ratios of 4-5:1) enhanced the interaction of LDL with cultured human fibroblasts by 7-12-fold. Participation by both receptors and cell surface heparin sulfate proteoglycans was observed. When a preformed peptide/125I-LDL complex was injected intravenously into C57BL/6J apoE-deficient mice, its rate of removal was threefold higher than that of 125I-LDL alone. The liver and the spleen were major tissue distribution sites. Intravenous administration of free acetylated peptide resulted in a 30% reduction in total plasma cholesterol within 3-30 min, which reflected a 40-50% and 20-26% reduction in very low density lipoproteins and intermediate density lipoproteins, respectively....Continue Reading

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Citations

Apr 14, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kirsty GreenowDipak P Ramji
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