title: Suppressive effects of iron overloading on vascular calcification in uremic rats.
abstract: BACKGROUND
  Medial vascular calcification is a specific complication in chronic kidney disease (CKD) patients although its pathogenesis is poorly understood. The administration of iron (Fe), generally used for the treatment of anemia in CKD patients, induces oxidative stress. Fe loading possibly affects the progress of vascular calcification in uremia. We investigated the effect of Fe on vascular calcification and its mechanism in uremic rats.
  
  
  METHODS
  Thirty-two rats were divided into four groups: untreated rats (controls), rats fed a standard diet with Fe administration (Fe group), rats fed an adenine-enriched diet (uremic group), and rats fed an adenine-enriched diet with Fe administration (uremic + Fe group). Iron dextran was administered once a week for 5 weeks intraperitoneally. Morphological alterations and vascular calcification-associated factors in the aortic wall were evaluated.
  
  
  RESULTS
  No aortic calcification was observed in the control group although uremic rats developed severe vascular calcification. Fe loading suppressed vascular calcification in the uremic groups. Expressions of runt-related transcription factor 2 (Runx2), single-strand (ss)DNA and phosphate transporter (Pit)-1 were increased in the uremic rats compared to the control rats. In the uremic group, Fe administration did not show any effect on ssDNA expression, but reduced Runx2 and Pit-1 expressions.
  
  
  CONCLUSIONS
  Fe suppressed the development of vascular calcification through the prevention of Pit-1 and vascular smooth muscle cell osteoblastic transdifferentiation.
authors: Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors: Takuya
authors: T
authors: Seto
authors: Chieko
authors: C
authors: Hamada
authors: Yasuhiko
authors: Y
authors: Tomino
mesh_terms: D000225:Adenine; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis / Q000235:genetics; D003404:Creatinine / Q000097:blood; D004277:DNA, Single-Stranded / Q000032:analysis; D005293:Ferritins / Q000097:blood; D007501:Iron / Q000097:blood; D007505:Iron-Dextran Complex / Q000008:administration & dosage*; D008297:Male; D010710:Phosphates / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000032:analysis / Q000235:genetics; D014168:Transferrin / Q000378:metabolism; D017540:Tunica Media / Q000473:pathology*; D014511:Uremia / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D061205:Vascular Calcification / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D004277:DNA, Single-Stranded; D010710:Phosphates; D012333:RNA, Messenger; C493717:Runx2 protein, rat; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D014168:Transferrin; D007505:Iron-Dextran Complex; D005293:Ferritins; D003404:Creatinine; D007501:Iron; D000225:Adenine