The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit

• Published in: Lipids in health and disease Vol. 10; no. 1; p. 224
• Main Authors: Di Bartolo, Belinda A, Vanags, Laura Z, Tan, Joanne Tm, Bao, Shisan, Rye, Kerry-Anne, Barter, Philip J, Bursill, Christina A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.11.2011; BioMed Central; BMC
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - pharmacology; 1,2-Dipalmitoylphosphatidylcholine - therapeutic use; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Aorta, Thoracic - drug effects; Aorta, Thoracic - pathology; Apolipoprotein A-I - pharmacology; Apolipoprotein A-I - therapeutic use; apolipoproteinA-I; apolipoproteinA-I mimetic peptides; Apolipoproteins; Cells, Cultured; Cholesterol; Cholesterol - blood; Chronic Disease; Coronary vessels; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Experiments; Gene Expression - drug effects; High density lipoproteins; Humans; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); Lipids; Lipoproteins; Lipoproteins, HDL - pharmacology; Lipoproteins, HDL - therapeutic use; Male; Peptides; Peptides - pharmacology; Peptides - therapeutic use; Phospholipids; Physiological aspects; Plasma; Rabbits; Random Allocation; Sphingomyelins - pharmacology; Sphingomyelins - therapeutic use; Studies; TNF inhibitors; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; vascular inflammation; Veins & arteries; Australia
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511x-10-224

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. 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. 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.