title: Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible role in plaque destabilization.
abstract: OBJECTIVE
  Based on its role in inflammation and matrix degradation, we hypothesized a role for osteoprotegerin (OPG), RANK, and RANK ligand (RANKL) in coronary artery disease.
  
  
  RESULTS
  We examined the expression of various members of the OPG/RANKL/RANK axis in patients with stable and unstable angina and in the atherosclerotic lesions of apolipoprotein E-deficient (apoE(-/-)) mice. Our findings were: (1) Serum levels of OPG were raised in patients with unstable angina (n=40), but not in those with stable angina (n=40), comparing controls (n=20); (2) mRNA levels of RANKL were increased in T-cells in unstable angina patients accompanied by increased expression of RANK in monocytes; (3) strong immunostaining of OPG/RANKL/RANK was seen within thrombus material obtained at the site of plaque rupture during acute myocardial infarction; (4) OPG/RANKL/RANK was expressed in the atherosclerotic plaques of apoE(-/-) mice, with RANKL located specifically to the plaques; and (5) RANKL enhanced the release of monocyte chemoattractant peptide-1 in mononuclear cells from unstable angina patients, and promoted matrix metalloproteinase (MMP) activity in vascular smooth muscle cells.
  
  
  CONCLUSIONS
  We show enhanced expression of the OPG/RANKL/RANK system both in clinical and experimental atherosclerosis, with enhanced T-cell expression of RANKL as an important feature of unstable disease.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway. wiggo.sandberg@klinmed.uio.no
authors.forename: Wiggo J
authors.initials: WJ
authors.lastname: Sandberg
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Erik
authors.initials: E
authors.lastname: Øie
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Olga
authors.initials: O
authors.lastname: Ovchinnikova
authors.forename: Anna-Karin L
authors.initials: AK
authors.lastname: Robertson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Müller
authors.forename: Anne G
authors.initials: AG
authors.lastname: Semb
authors.forename: Hanne
authors.initials: H
authors.lastname: Scholz
authors.forename: Arne K
authors.initials: AK
authors.lastname: Andreassen
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood* / Q000378:metabolism*; D012422:Rupture, Spontaneous / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D020782:Matrix Metalloproteinases