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Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice.

Abstract：

BACKGROUND:The novel phosphate binder sevelamer has been shown to prevent the progression of aortic and coronary calcification in uremic patients. Whether it also decreases the progression of atheromatous plaques is unknown. The aim of our study was to examine the effect of sevelamer administration on the development of atherosclerosis and aortic calcification in the uremic apolipoprotein E-deficient mouse as an established model of accelerated atherosclerosis. METHODS AND RESULTS:Female mice were randomly assigned to 4 groups: 2 groups of nonuremic mice (sevelamer versus control) and 2 groups of uremic mice (sevelamer versus control). Sevelamer was given at 3% with chow. The increases in serum phosphorus concentration and calcium-phosphorus product observed in uremic control mice were prevented by sevelamer. Serum total cholesterol was increased in the 2 uremic mouse groups and remained unchanged in response to sevelamer. After 8 weeks of sevelamer treatment, uremic mice exhibited a significantly lower degree of atherosclerosis (P<0.001) and vascular calcification than uremic control mice. Of interest, sevelamer exerted an effect on both intima and media calcification (P=0.005) in uremic mice. Among possible mechanisms involved, we found no evidence for the modulation by sevelamer of inflammation or selected uremic toxins. In contrast, nitrotyrosine staining as a measure of oxidative damage was significantly decreased in response to sevelamer treatment in control and uremic mice (P<0.005). CONCLUSIONS:Sevelamer delays not only vascular calcification but also atherosclerotic lesion progression in uremic apolipoprotein E-deficient mice. It opens the possibility of a cholesterol-independent action of sevelamer on atheroma formation via effects on mineral metabolism, oxidative stress, or both.

journal_name

Circulation

journal_title

Circulation

authors

Phan O,Ivanovski O,Nguyen-Khoa T,Mothu N,Angulo J,Westenfeld R,Ketteler M,Meert N,Maizel J,Nikolov IG,Vanholder R,Lacour B,Drüeke TB,Massy ZA

doi

10.1161/CIRCULATIONAHA105.541854

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

2875-82

issue

eissn

0009-7322

issn

1524-4539

pii

112/18/2875

journal_volume

112

pub_type

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Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice.