title: The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit.
abstract: BACKGROUND
  High-density lipoproteins (HDL) and their main apolipoprotein, apoA-I, exhibit anti-inflammatory properties. The development of peptides that mimic HDL apolipoproteins offers a promising strategy to reduce inflammatory disease. This study aimed to compare the anti-inflammatory effects of ETC-642, an apoA-I mimetic peptide, with that of discoidal reconstituted HDL (rHDL), consisting of full-length apoA-I complexed with phosphatidylcholine, in rabbits with chronic vascular inflammation.
  
  
  RESULTS
  New Zealand White rabbits (n = 10/group) were placed on chow supplemented with 0.2% (w/w) cholesterol for 6-weeks. The animals received two infusions of saline, rHDL (8 mg/kg apoA-I) or ETC-642 (30 mg/kg peptide) on the third and fifth days of the final week. The infusions of rHDL and ETC-642 were able to significantly reduce cholesterol-induced expression of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the thoracic aorta (p < 0.05). When isolated rabbit HDL was pre-incubated with human coronary artery endothelial cells (HCAECs), prior to stimulation with TNF-α, it was found that HDL from ETC-642 treated rabbits were more effective at inhibiting the TNF-α-induced increase in ICAM-1, VCAM-1 and p65 than HDL isolated from saline treated rabbits (p < 0.05). There were, however, no changes in HDL lipid composition between treatment groups.
  
  
  CONCLUSIONS
  Infusion of ETC-642 causes anti-inflammatory effects that are comparable to rHDL in an animal model of chronic vascular inflammation and highlights that apoA-I mimetic peptides present a viable strategy for the treatment of inflammatory disease.
authors: Lipid Research Group, Heart Research Institute, 7 Eliza St, Newtown, NSW 2042, Australia.
authors: Belinda A
authors: BA
authors: Di Bartolo
authors: Laura Z
authors: LZ
authors: Vanags
authors: Joanne Tm
authors: JT
authors: Tan
authors: Shisan
authors: S
authors: Bao
authors: Kerry-Anne
authors: KA
authors: Rye
authors: Philip J
authors: PJ
authors: Barter
authors: Christina A
authors: CA
authors: Bursill
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D016632:Apolipoprotein A-I / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D013109:Sphingomyelins / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; C568357:ETC 642; D008075:Lipoproteins, HDL; D010455:Peptides; D013109:Sphingomyelins; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol