title: Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE-/-) mice with chronic renal failure.
abstract: BACKGROUND
  In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF).
  
  
  METHODS
  Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods.
  
  
  RESULTS
  Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p<0.05) and non-plaque-associated calcification surface (p<0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions.
  
  
  CONCLUSIONS
  In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CRF.
authors.affiliation: Inserm, Unit 845, Necker Hospital, Université Paris V, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Phan
authors.forename: Ognen
authors.initials: O
authors.lastname: Ivanovski
authors.forename: Igor G
authors.initials: IG
authors.lastname: Nikolov
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Joki
authors.forename: Julien
authors.initials: J
authors.lastname: Maizel
authors.forename: Loïc
authors.initials: L
authors.lastname: Louvet
authors.forename: Maud
authors.initials: M
authors.lastname: Chasseraud
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen-Khoa
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001018:Aortic Diseases / Q000139:chemically induced* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D002114:Calcinosis / Q000139:chemically induced* / Q000473:pathology; D002119:Calcium Carbonate / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D007676:Kidney Failure, Chronic / Q000150:complications*; D051379:Mice
chemical_list: D001057:Apolipoproteins E; D002119:Calcium Carbonate