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: Igor G Nikolov, Nobuhiko Joki, Thao Nguyen-Khoa, Ida Chiara Guerrera, Julien Maizel, Joyce Benchitrit, Luciene Machado dos Reis, Aleksander Edelman, Bernard Lacour, Vanda Jorgetti, Tilman B Drüeke, Ziad A Massy
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 2 Pg. 505-13 (Feb 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 21705467 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Polyamines
• lanthanum carbonate
• Lanthanum
• Collagen
• Sevelamer

Topics

• Analysis of Variance
• Animals
• Aorta (drug effects, pathology)
• Apolipoproteins E (deficiency)
• Atherosclerosis (blood, prevention & control)
• Blood Chemical Analysis
• Bone Density (physiology)
• Collagen (analysis, metabolism)
• Disease Models, Animal
• Disease Progression
• Female
• Immunohistochemistry
• Lanthanum (metabolism, pharmacology)
• Mice
• Mice, Inbred Strains
• Polyamines (metabolism, pharmacology)
• Random Allocation
• Reference Values
• Renal Insufficiency, Chronic (drug therapy, physiopathology)
• Sevelamer
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Uremia (drug therapy, physiopathology)
• Vascular Calcification (prevention & control)