title: Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats.
abstract: BACKGROUND
  Stage 5 chronic kidney disease (CKD) is associated with enhanced aortic calcification. The aim of this study was to determine if the administration of indoxyl sulphate (IS), a uraemic toxin, stimulates the progression of aortic calcification.
  
  
  METHODS
  The rat groups consisted of (i) Dahl salt-resistant normotensive rats (DR) with intake of 0.3% salt, (ii) Dahl salt-sensitive hypertensive rats (DS) with intake of 2.0% salt and (iii) Dahl salt-sensitive hypertensive IS-administered rats (DS-IS) with intake of 2.0% salt and 200 mg/kg of IS in water. After 30 weeks, their aortic and kidney tissues were excised for histological and immunohistochemical analyses.
  
  
  RESULTS
  Severe vascular calcification was observed by von Kossa staining in the arcuate aorta of all the DS-IS rats, but hardly in DS or DR rats. Immunohistochemistry demonstrated that osteopontin, core binding factor 1 (Cbfal), alkaline phosphatase (ALP), osteocalcin, IS and organic anion transporter (OAT) 3 were colocalized in the cells embedded in the aortic calcification area of DS-IS rats. Wall thickness was significantly increased in arcuate, thoracic and abdominal aortas of DS-IS rats compared with DS and DR rats. DS-IS rats showed significantly increased extent of glomerular hypertrophy, mesangial expansion, Masson's trichrome-positive tubulointerstitial area and glomerular and tubulointerstitial expression of transforming growth factor-ssl as compared with DS and DR rats.
  
  
  CONCLUSIONS
  IS induced aortic calcification with expression of osteoblast-specific proteins and aortic wall thickening. IS is not only a nephrotoxin but also a vascular toxin, and may contribute to the progression of aortic calcification in stage 5 CKD patients.
authors.affiliation: Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Ayinuer
authors.initials: A
authors.lastname: Adijiang
authors.forename: Sumie
authors.initials: S
authors.lastname: Goto
authors.forename: Satsuki
authors.initials: S
authors.lastname: Uramoto
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Nishijima
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001018:Aortic Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D050660:Core Binding Factors / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D007200:Indican; D007678:Kidney Glomerulus / Q000473:pathology; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary
chemical_list: D050660:Core Binding Factors; D029362:Organic Anion Transporters, Sodium-Independent; C421143:Slco1a5 protein, rat; D017673:Sodium Chloride, Dietary; D053495:Osteopontin; D007200:Indican