title: High phosphate feeding induced arterial medial calcification in uremic rats: roles of Lanthanum carbonate on protecting vasculature.
abstract: OBJECTIVE
  High cardiovascular mortality in patients with end-stage renal disease is closely associated with arterial medial calcification (AMC) caused by hyperphosphatemia, the mechanism of which associated hormones (FGF-23, klotho) and osteochondrogenic events is unclear. We examined the effect of Lanthanum carbonate on AMC via regulating the abnormalities in phosphorus metabolism of uremic rats.
  
  
  METHODS
  45 healthy SD rats were randomly divided into 3 groups: Normal group (n=15), CRF group (n=15), CRF diet supplemented with 2% La (n=15). AMC in great arteries were evaluated by VonKossa. Osteochondrogenic specific genes were analyzed by Immunohistochemistry and qRT-PCR. Serum FGF-23 and klotho levels were detected by ELISA kit.
  
  
  RESULTS
  Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter became hypophosphatemic (2.92 ± 0.73 mmol/L vs CRF group, p<0.01) at week 10. Inhibitory effect of 2%La on development of AMC was reflected by downregulated Runx2, Osterix, BSP, Osteocalcin and collagenII and a reduction of FGF-23 at week 4(vs CRF group, p<0.01) but not week 10.
  
  
  CONCLUSIONS
  Beneficial effects of Lanthanum carbonate on progression of AMC in CRF could be mainly due to the decreased phosphate retention and FGF-23 in early stage and likewise a reduction of bone-associated proteins via osteochondrogenic pathway. Lanthanum carbonate has no effect on soluble klotho and serum FGF-23 in late stage of CRF.
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Shandong 250021, P.R. China.
authors.forename: Che
authors.initials: C
authors.lastname: Yu
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Javed
authors.initials: J
authors.lastname: Akhtar
authors.forename: Haiping
authors.initials: H
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D024043:Collagen Type II / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis; D054559:Hyperphosphatemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D058574:Integrin-Binding Sialoprotein / Q000096:biosynthesis; D007811:Lanthanum / Q000627:therapeutic use*; D008297:Male; D015675:Osteocalcin / Q000096:biosynthesis; D010710:Phosphates / Q000097:blood; D016226:Phosphorus, Dietary / Q000009:adverse effects*; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis; D017540:Tunica Media / Q000473:pathology; D014511:Uremia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D010710:Phosphates; D016226:Phosphorus, Dietary; C493717:Runx2 protein, rat; C495181:Sp7 protein, rat; D014157:Transcription Factors; D015675:Osteocalcin; C119467:lanthanum carbonate; D005346:Fibroblast Growth Factors; D007811:Lanthanum; D000089703:Fibroblast Growth Factor-23
keywords: Arterial medial calcification; Chronic renal failure; FGF-23; Hyperphosphatemia; Klotho; Lanthanum carbonate