title: Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF).
  
  
  METHODS
  Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%).
  
  
  RESULTS
  Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%.
  
  
  CONCLUSIONS
  The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.
authors.affiliation: Inserm ERI-12, UFR de Médecine/Pharmacie, University of Picardie, Amiens, France.
authors.forename: Igor G
authors.initials: IG
authors.lastname: Nikolov
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Joki
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen-Khoa
authors.forename: Ida Chiara
authors.initials: IC
authors.lastname: Guerrera
authors.forename: Julien
authors.initials: J
authors.lastname: Maizel
authors.forename: Joyce
authors.initials: J
authors.lastname: Benchitrit
authors.forename: Luciene
authors.initials: L
authors.lastname: Machado dos Reis
authors.forename: Aleksander
authors.initials: A
authors.lastname: Edelman
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
authors.forename: Vanda
authors.initials: V
authors.lastname: Jorgetti
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000517:prevention & control*; D001774:Blood Chemical Analysis; D015519:Bone Density / Q000502:physiology; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D007811:Lanthanum / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D000069603:Sevelamer; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014511:Uremia / Q000188:drug therapy / Q000503:physiopathology; D061205:Vascular Calcification / Q000517:prevention & control*
chemical_list: D001057:Apolipoproteins E; D011073:Polyamines; C119467:lanthanum carbonate; D007811:Lanthanum; D003094:Collagen; D000069603:Sevelamer