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High levels and inflammatory effects of soluble CXCL16 in coronary artery disease - down-regulatory effects of statins

  1. Camilla Smith1,
  2. Bente Halvorsen1,
  3. Kari Otterdal1,
  4. Torgun Wæhre1,
  5. Arne Yndestad1,
  6. Børre Fevang1,
  7. Wiggo J. Sandberg1,
  8. Unni M. Breland1,
  9. Stig S. Frøland1,2,
  10. Erik Øie3,
  11. Lars Gullestad3,
  12. Jan K. Damås1,2 and
  13. Pål Aukrust1,2
  1. 1Research Institute for Internal Medicine,
    Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo
    , Norway
  2. 2
    Section of Clinical Immunology and Infectious Diseases, and Rikshospitalet-Radiumhospitalet Medical Center
    , University of Oslo, Norway
  3. 3
    Department of Cardiology
    , Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Norway
  1. Address for correspondence: Pål Aukrust, MD, PhD
    Section of Clinical Immunology and Infectious Diseases Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo
    , Norway Phone: 47-23070000, Fax: 47-23073630, e-mail: pal.aukrust{at}rikshospitalet.no
  • Received March 7, 2008.
  • Accepted March 10, 2008.

ABSTRACT

Aims CXC ligand 16 (CXCL16) may be involved in inflammation and lipid metabolism, and we hypothesized a role for this chemokine in coronary artery disease (CAD).

Methods We performed clinical studies in CAD patients as well as experimental studies in cells with relevance to atherogenesis (i.e., endothelial cells, vascular smooth muscle cells, and peripheral blood mononuclear cells [PBMC]). We also examined the ability of HMG-CoA reductase inhibitors (statins) to modulate CXCL16 levels both in vivo and in vitro.

Results Our main findings were: 1) Patients with stable (n=40) and unstable (n=40) angina had elevated plasma levels of CXCL16 compared to controls (n=20). 2) Low-dose simvastatin (20 mg qd, n=15) and high-dose atorvastatin (80 mg qd, n=9) down-regulated plasma levels of CXCL16 during 6 months of therapy. 3) In vitro, atorvastatin significantly decreased the interleukin (IL)-1β-mediated release of CXCL16 from PBMC and endothelial cells. 4) The attenuating effect of atorvastatin on the IL-1β-mediated release of CXCL16 in PBMC seems to involve post-transcriptional modulation as well as down-regulation of CXCL16 release through inhibition of the protease ADAM10. 5) Soluble CXCL16 increased the release of IL-8, monocyte chemoattractant peptide 1, and matrix metalloproteinases in vascular smooth muscle cells and increased the release of IL-8 and monocyte chemoattractant peptide 1 in PBMC, with particularly enhancing effects in cells from CAD patients.

Conclusion Our findings suggest that soluble CXCL16 could be linked to atherogenesis not only as a marker of inflammation, but also as a potential inflammatory mediator.

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    This Article

    1. Cardiovasc Res (2008) doi: 10.1093/cvr/cvn071 First published online: March 13, 2008
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