Anti-inflammatory effects of apolipoprotein A-I in the rabbit

Sanjay Patel, Belinda A. Di Bartolo, Shirley Nakhla, Alison K. Heather, Todd W. Mitchell, Wendy Jessup, David S. Celermajer, Philip J. Barter, Kerry Anne Rye

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Objective: Infusions of apoA-I in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins, (A-I)rHDL, markedly inhibit acute vascular inflammation in normocholesterolemic New Zealand White (NZW) rabbits. This effect is apparent even when apoA-I is administered 24 h prior to the inflammatory insult. The present study asks if this benefit is related to an improved anti-inflammatory capacity of the high-density lipoprotein (HDL) fraction, or to increased arterial expression of genes that inhibit inflammation. Methods and results: The ability of apoA-I to increase the anti-inflammatory capacity of HDL was assessed by infusing normocholesterolemic NZW rabbits with saline, lipid-free apoA-I or (A-I)rHDL. The infused apoA-I incorporated rapidly into the rabbit HDL fraction. The animals were sacrificed at 5 or 360 min post-infusion and plasma was collected. HDL were isolated by ultracentrifugation and incubated with cytokine-activated cultured human coronary artery endothelial cells. HDL from animals sacrificed at 5 min post-apoA-I infusion had a slightly enhanced anti-inflammatory capacity relative to HDL from the saline-infused animals. The anti-inflammatory capacity of HDL from the animals sacrificed at 360 min post-apoA-I infusion was comparable to that of HDL from the saline-infused animals. The effect of (A-I)rHDL infusions on arterial 3β-hydroxysteroid-Δ24 reductase (DHCR24) and endothelial adhesion molecule expression was investigated in cholesterol-fed NZW rabbits. Relative to animals infused with saline, (A-I)rHDL infusions decreased aortic VCAM-1 and ICAM-1 protein expression by 73 and 54%, respectively (p< 0.05), and increased DHCR24 mRNA levels by 56% (p< 0.0001). Conclusion: ApoA-I inhibits vascular inflammation in NZW rabbits, at least in part, by increasing DHCR24 expression.

Original languageEnglish
Pages (from-to)392-397
Number of pages6
JournalAtherosclerosis
Volume212
Issue number2
DOIs
Publication statusPublished - Oct 2010

Keywords

  • ApoA-I
  • DHCR24
  • HDL
  • ICAM-1
  • Inflammation
  • VCAM-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this