title: Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis.
abstract: OBJECTIVE
  The aim of this study was to compare the concentration of osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL), and osteopontin (OPN) in stable (asymptomatic) and unstable (symptomatic) carotid atherosclerosis. In addition, we were interested in the effect of angiotensin II blockade on the secretion of these proteins by unstable atherosclerosis.
  
  
  METHODS
  Endarterectomy samples removed from patients with recent (within 6 weeks) or no previous focal neurological symptoms were assessed by immunohistochemistry, Western analysis, and explant culture. Concentrations of OPG, RANKL, and OPN were measured by mean optical density (MOD), densitometry of protein bands, and enzyme-linked immunosorbent assay of supernatants from explant culture, and compared between symptomatic and asymptomatic patients.
  
  
  RESULTS
  The concentration of OPG and OPN within the proximal internal carotid (PIC) part of the endarterectomy specimen removed from symptomatic patients was elevated 2- and 4-fold, respectively. Although the concentration of RANKL did not differ according to patients' symptoms, the quantity of OPG secreted by explants of the PIC was greater in explants from symptomatic patients and could be significantly reduced within 48 hours of incubation with the angiotensin II blocker irbesartan.
  
  
  CONCLUSIONS
  OPG and OPN are upregulated in symptomatic human carotid atherosclerosis with possible implications for plaque stability. Angiotensin II blockade is able to downregulate OPG secretion in vitro.
authors.affiliation: The Vascular Biology Unit, James Cook University, Townsville, Queensland 4811, Australia. Jonathan.Golledge@jcu.edu.au
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Moira
authors.initials: M
authors.lastname: McCann
authors.forename: Simone
authors.initials: S
authors.lastname: Mangan
authors.forename: Alfred
authors.initials: A
authors.lastname: Lam
authors.forename: Mirko
authors.initials: M
authors.lastname: Karan
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001713:Biphenyl Compounds / Q000627:therapeutic use; D015153:Blotting, Western; D016893:Carotid Stenosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D000077405:Irbesartan; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D053495:Osteopontin; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D013777:Tetrazoles / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D001713:Biphenyl Compounds; 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; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D013777:Tetrazoles; D053495:Osteopontin; D000804:Angiotensin II; D000077405:Irbesartan