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

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-alpha stimulation. Monocyte adhesion was investigated by pre-incubating HCAECs with rHDL or ETC-642, stimulating with TNF-alpha 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-alpha-induced THP-1 monocyte adhesion (p < 0.01). Furthermore, ETC-642 and rHDL treatment reduced TNF-alpha induced mRNA levels of inflammatory markers VCAM-1, fractalkine, MCP-1 and the p65 subunit of NF-kappa B (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-kappa B signaling pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.