title: The apolipoprotein A-I mimetic peptide ETC-642 exhibits anti-inflammatory properties that are comparable to high density lipoproteins.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lipid Research Group, Heart Research Institute, Sydney, Australia.
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Di Bartolo
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Alison K
authors.initials: AK
authors.lastname: Heather
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Christina
authors.initials: C
authors.lastname: Bursill
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000097:blood*; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000235:genetics; D054428:Chemokine CX3CL1 / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D018716:Molecular Mimicry; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013109:Sphingomyelins / Q000008:administration & dosage / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; C568356:ESP 24218; C568357:ETC 642; D036341:Intercellular Signaling Peptides and Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D010455:Peptides; C498143:RELA protein, human; D012333:RNA, Messenger; D013109:Sphingomyelins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C034366:discoidal lipoproteins; D018799:Intercellular Adhesion Molecule-1; D015060:1,2-Dipalmitoylphosphatidylcholine