The apolipoprotein A-I mimetic peptide ETC-642 exhibits anti-inflammatory properties that are comparable to high density lipoproteins

Belinda A. Di Bartolo, Stephen J. Nicholls, Shisan Bao, Kerry Anne Rye, Alison K. Heather, Philip J. Barter, Christina Bursill

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40 Citations (Scopus)

Abstract

Objectives: Mimetic peptides of apolipoprotein A-I (apoA-I) present a new strategy for promoting the biological activity of high density lipoproteins (HDL). This study aimed to compare the anti-inflammatory effects of ETC-642, a new apoA-I mimetic peptide, with discoidal reconstituted HDL (rHDL). Methods: New Zealand White rabbits (n = 42) received daily infusions of saline, rHDL or discoidal complexes of an amphipathic peptide, ETC-642 (1-30. mg/kg), prior to insertion of non-occlusive carotid collars. Human coronary artery endothelial cells (HCAECs) were pre-incubated with ETC-642 or rHDL before TNF-α stimulation. Monocyte adhesion was investigated by pre-incubating HCAECs with rHDL or ETC-642, stimulating with TNF-α and incubating with THP-1 monocytes. Results: Infusion of ETC-642 resulted in dose-dependent reductions of collar-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the artery wall (p< 0.05). Pre-incubation of HCAECs with ETC-642 and rHDL reduced TNF-α-induced THP-1 monocyte adhesion (p< 0.01). Furthermore, ETC-642 and rHDL treatment reduced TNF-α induced mRNA levels of inflammatory markers VCAM-1, fractalkine, MCP-1 and the p65 subunit of NF-κB (p< 0.05). Conclusion: These studies demonstrate that ETC-642 exhibits anti-inflammatory properties that are comparable to apoA-I both in vivo and in vitro and that these effects are mediated via the NF-κB signaling pathway.

Original languageEnglish
Pages (from-to)395-400
Number of pages6
JournalAtherosclerosis
Volume217
Issue number2
DOIs
Publication statusPublished - 1 Aug 2011
Externally publishedYes

Keywords

  • Adhesion molecules
  • Apolipoprotein A-I
  • Apolipoprotein A-I mimetic peptides
  • Chemokines
  • Inflammation

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