title: Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy.
abstract: OBJECTIVE
  Recent data derived primarily from studies in animal models suggest that fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis. We, therefore, hypothesized that enhanced CX3CL1/CX3CR1 expression may promote atherogenesis in patients with coronary artery disease (CAD).
  
  
  RESULTS
  We examined the plasma levels of CX3CL1 and CX3CR1 expression in peripheral blood mononuclear cells (PBMC) in various CAD populations (30 patients with previous myocardial infarction, 40 patients with stable angina, 40 patients with unstable angina, and a total of 35 controls) and used various experimental approaches to characterize CX3CL1-mediated leukocyte responses. We found that the plasma levels of CX3CL1 are greatly increased in CAD, particularly in unstable disease. The parallel increase of CX3CR1 expression in PBMC was predominantly attributable to an expansion of the (CX3CR1+)(CD3+)(CD8+) T cell subset and was associated with enhanced chemotactic, adhesive, and inflammatory responses to CX3CL1. Statin therapy for 6 months reduced the expression of CX3CL1 and CX3CR1, reaching statistical significance for both parameters only during aggressive (atorvastatin, 80 mg qd) but not conventional (simvastatin, 20 mg qd) therapy. Consequently, the functional responses of the PBMC to CX3CL1 including migration, adhesion, and secretion of interleukin-8 were attenuated by the treatments.
  
  
  CONCLUSIONS
  Our results suggest that the CX3CL1/CX3CR1 dyad may contribute to atherogenesis and plaque destabilization in human CAD.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Agnes
authors.initials: A
authors.lastname: Boullier
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Wiggo J
authors.initials: WJ
authors.lastname: Sandberg
authors.forename: Simone
authors.initials: S
authors.lastname: Green
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
mesh_terms: D000789:Angina, Unstable / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000069059:Atorvastatin; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics* / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011758:Pyrroles / Q000008:administration & dosage*; D019707:Receptors, Chemokine / Q000235:genetics*; D019821:Simvastatin / Q000008:administration & dosage; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016209:Interleukin-8; D008565:Membrane Proteins; D011758:Pyrroles; D019707:Receptors, Chemokine; D000069059:Atorvastatin; D019821:Simvastatin