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

Belinda A. Di Bartolo, Laura Z. Vanags, Joanne Tm Tan, Shisan Bao, Kerry Anne Rye, Philip J. Barter, Christina A. Bursill

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

LanguageEnglish
Number of pages1
JournalLipids in Health and Disease
Volume10
DOIs
Publication statusPublished - 1 Dec 2011

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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