High-density lipoproteins suppress chemokines and chemokine receptors in vitro and in vivo

Christina A. Bursill, Maria L. Castro, Douglas T. Beattie, Shirley Nakhla, Emiel Van Der Vorst, Alison K. Heather, Philip J. Barter, Kerry Anne Rye

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Objective: To investigate whether high-density lipoproteins (HDLs) suppress chemokine (CCL2, CCL5, and CX3CL1) and chemokine receptor (CCR2 and CX3CR1) expression, a mechanism for the atheroprotective properties of HDLs. Methods and Results: Apolipoprotein (apo) E-/- mice were fed a high-fat diet for 12 weeks. Before being euthanized, the mice received 5 consecutive daily injections of lipid-free apoA-I, 40 mg/kg, or saline (control). The injection of apoA-I reduced CCR2 and CX3CR1 expression in plaques compared with controls (P<0.05). ApoA-I-injected mice had lower plasma CCL2 and CCL5 levels. Hepatic CCL2, CCL5, and CX3CL1 levels were also reduced (P<0.05). In vitro studies found that reconstituted HDL (rHDL) reduced monocyte CCR2 and CX3CR1 expression and inhibited their migration toward CCL2 and CX3CL1 (P<0.05). Preincubation with rHDL reduced CCL2, CCL5, and CX3CL1 expression in monocytes and human coronary artery endothelial cells. The stimulation of CX3CR1 with peroxisome proliferator-activated receptor γ agonist CAY10410 was suppressed by preincubation with rHDL but did not affect the peroxisome proliferator-activated receptor γ antagonist (GW9664)-mediated increase in CCR2. In monocytes and human coronary artery endothelial cells, rHDL reduced the expression of the nuclear p65 subunit, IκB kinase activity, and the phosphorylation of IκBα (P<0.05). Conclusion: Lipid-free apoA-I and rHDL reduce the expression of chemokines and chemokine receptors in vivo and in vitro via modulation of nuclear factor κB and peroxisome proliferator-activated receptor γ.

Original languageEnglish
Pages (from-to)1773-1778
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number9
DOIs
Publication statusPublished or Issued - Sep 2010

Keywords

  • atherosclerosis
  • chemokine receptors
  • chemokines
  • high-density lipoproteins
  • inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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