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Am J Physiol Renal Physiol 293: F1325-F1331, 2007. First published August 8, 2007; doi:10.1152/ajprenal.00039.2007
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Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

Christian A. Bang,1 Susanne Bro,1,2 Emil D. Bartels,1 Tanja X. Pedersen,1 and Lars B. Nielsen1,3

Departments of 1Clinical Biochemistry and 2Nephrology, Rigshospitalet, and 3Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Submitted 22 January 2007 ; accepted in final form 24 July 2007

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild-type C57BL/6J mice. Uremia was induced by nephrectomy (NX) and increased plasma urea and creatinine concentrations 2.5- to 4.5-fold; control mice were sham operated. After NX, mice were fed a Western-type diet or the same diet with 0.5% cholic acid. Cholic acid-fed NX mice did not thrive and were killed. In NX mice fed the Western-type diet (n = 7), the total plasma cholesterol concentration was similar to that in sham mice (n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham mice. Plasma concentrations of sICAM-1 and sVCAM-1 and aortic mRNA expression of ICAM-1 and VCAM-1 did not differ between NX and sham mice. Twenty-six weeks after NX, the average oil red O-stained area of the aortic root was similar in NX and sham mice fed the Western-type diet, while it was increased in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition.

inflammation; serum amyloid A



Address for reprint requests and other correspondence: L. B. Nielsen, Dept. of Clinical Biochemistry, KB3011, Rigshospitalet, Univ. of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark (e-mail: larsbo{at}rh.dk)







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