title: A potential role of the CXC chemokine GROalpha in atherosclerosis and plaque destabilization: downregulatory effects of statins.
abstract: OBJECTIVE
  We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis.
  
  
  RESULTS
  GROalpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROalpha was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GROalpha was among the 10 most differentially expressed transcripts comparing peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) and healthy controls. (2) Both patients with stable (n=41) and particularly those with unstable (n=47) angina had increased plasma levels of GROalpha comparing controls (n=20). (3) We found increased expression of GROalpha within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GROalpha enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GROalpha levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GROalpha in endothelial cells involved increased storage and reduced secretion of GROalpha.
  
  
  CONCLUSIONS
  GROalpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway. Unni.Mathilde.Breland@rr-research.no
authors.forename: Unni M
authors.initials: UM
authors.lastname: Breland
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Johanna
authors.initials: J
authors.lastname: Hol
authors.forename: Erik
authors.initials: E
authors.lastname: Øie
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Paulsson-Berne
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Wiggo J
authors.initials: WJ
authors.lastname: Sandberg
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Gøran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000789:Angina, Unstable / Q000378:metabolism / Q000473:pathology; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D014471:Umbilical Veins / Q000378:metabolism / Q000473:pathology
chemical_list: D054360:Chemokine CXCL1; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1