Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I.

Academic Article

Abstract

  • 4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is active in vivo at nanomolar concentrations in the presence of a large molar excess of apoA-I. Physiologic concentrations ( approximately 35 microM) of human apoA-I did not inhibit the production of LDL-induced monocyte chemotactic activity by human aortic endothelial cell cultures, but adding nanomolar concentrations of 4F in the presence of approximately 35 microM apoA-I significantly reduced this inflammatory response. We analyzed lipid binding by surface plasmon resonance. The anti-inflammatory 4F peptide bound oxidized lipids with much higher affinity than did apoA-I. Initially, we examined the binding of PAPC (1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine) and observed that its oxidized products bound 4F with an affinity that was approximately 4-6 orders of magnitude higher than that of apoA-I. This high binding affinity was confirmed in studies with defined lipids and phospholipids. 3F-2 and 3F(14) are also amphipathic alpha-helical octadecapeptides, but 3F-2 inhibits atherosclerosis in mice and 3F(14) does not. Like 4F, 3F-2 also bound oxidized phospholipids with very high affinity, whereas 3F(14) resembled apoA-I. The extraordinary ability of 4F to bind pro-inflammatory oxidized lipids probably accounts for its remarkable anti-inflammatory properties.
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    Keywords

  • Amino Acid Sequence, Anti-Inflammatory Agents, Non-Steroidal, Apolipoprotein A-I, Cells, Cultured, Humans, Inflammation Mediators, Lipid Peroxidation, Molecular Mimicry, Molecular Sequence Data, Peptides, Phospholipids, Protein Binding
  • Digital Object Identifier (doi)

    Author List

  • Van Lenten BJ; Wagner AC; Jung C-L; Ruchala P; Waring AJ; Lehrer RI; Watson AD; Hama S; Navab M; Anantharamaiah GM
  • Start Page

  • 2302
  • End Page

  • 2311
  • Volume

  • 49
  • Issue

  • 11