title: High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins.
abstract: OBJECTIVE
  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).
  
  
  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)-1beta-mediated release of CXCL16 from PBMC and endothelial cells; (iv) attenuating effect of atorvastatin on the IL-1beta-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet Medical Center, University of Oslo, Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Børre
authors.initials: B
authors.lastname: Fevang
authors.forename: Wiggo J
authors.initials: WJ
authors.lastname: Sandberg
authors.forename: Unni M
authors.initials: UM
authors.lastname: Breland
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Erik
authors.initials: E
authors.lastname: Oie
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D016022:Case-Control Studies; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C423727:CXCL16 protein, human; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016209:Interleukin-8; D011758:Pyrroles; D051116:Receptors, Scavenger; D000069059:Atorvastatin; D019821:Simvastatin