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

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• 作者：Belinda A Di Bartolo (1)
  Laura Z Vanags (2)
  Joanne TM Tan (2)
  Shisan Bao (3)
  Kerry-Anne Rye (1) (4) (5)
  Philip J Barter (1) (4)
  Christina A Bursill (2) (4)
  
• 关键词：High ; density lipoproteins ; apolipoproteinA ; I ; apolipoproteinA ; I mimetic peptides ; vascular inflammation ; rabbits ; intracellular cell adhesion molecule ; 1 (ICAM ; 1) and vascular cell adhesion molecule ; 1 (VCAM ; 1)
• 刊名：Lipids in Health and Disease
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：10
• 期：1
• 全文大小：371KB
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• 作者单位：Belinda A Di Bartolo (1)
  Laura Z Vanags (2)
  Joanne TM Tan (2)
  Shisan Bao (3)
  Kerry-Anne Rye (1) (4) (5)
  Philip J Barter (1) (4)
  Christina A Bursill (2) (4)
  
  1. Lipid Research Group, Heart Research Institute, 7 Eliza St, Newtown, NSW, 2042, Australia
  2. Immunobiology Unit, Heart Research Institute, 7 Eliza St, Newtown, NSW, 2042, Australia
  3. Discipline of Pathology, University of Sydney, Camperdown, NSW, 2050, Australia
  4. Department of Medicine, University of Sydney, Camperdown, NSW, 2050, Australia
  5. Department of Medicine, University of Melbourne, Parkville, Victoria, 3010, Australia
  

文摘

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.