Cardiovascular Research Advance Access first published online on March 13, 2008
This version [Corrected Proof] published online on April 8, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn071
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High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins
1 Research Institute for Internal Medicine, Rikshospitalet Medical Center, University of Oslo, Oslo, Norway
2 Section of Clinical Immunology and Infectious Diseases, Rikshospitalet Medical Center, University of Oslo, Sognsvannsveien 20, N-0027 Oslo, Norway
3 Department of Cardiology, Rikshospitalet Medical Center, University of Oslo, Oslo, Norway
* Corresponding author. Tel: +47 23070000; fax: +47 23073630. E-mail address: pal.aukrust{at}rikshospitalet.no
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 and results: 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 (SMC), 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. Our main findings were: (i) patients with stable (n = 40) and unstable (n = 40) angina had elevated plasma levels of CXCL16 compared with controls (n = 20); (ii) 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; (iii) in vitro, atorvastatin significantly decreased the interleukin (IL)-1β-mediated release of CXCL16 from PBMC and endothelial cells; (iv) 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 a disintegrin and metalloproteinase 10 (ADAM10); (v) soluble CXCL16 increased the release of IL-8, monocyte chemoattractant peptide 1, and matrix metalloproteinases in vascular SMC 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.
KEYWORDS Atherosclerosis; Chemokines; Coronary artery disease; Statins
Time for primary review: 16 days