This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/3/570    most recent 01.ATV.0000201060.47945.cbv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bro, S. Articles by Nielsen, L. B. Search for Related Content PubMed PubMed Citation Articles by Bro, S. Articles by Nielsen, L. B.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:570.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Uremia-Specific Effects in the Arterial Media During Development of Uremic Atherosclerosis in Apolipoprotein E–Deficient Mice

Susanne Bro; Rehannah Borup; Claus B. Andersen; Flemming Moeller; Klaus Olgaard; Lars B. Nielsen

From the Departments of Nephrology (S.B., K.O.), Clinical Biochemistry (S.B., R.B., F.M., L.B.N.), and Pathology (C.B.A.), Rigshospitalet, University of Copenhagen, Denmark.

Correspondence to Susanne Bro, Department of Nephrology P 2131, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail susannebro{at}dadlnet.dk

Objective— Uremia accelerates formation of atherosclerosis-like lesions in apolipoprotein E–deficient (apoE^–/–) mice. In this study, we compared gene expression patterns in classical and uremic atherosclerosis.

Methods and Results— High-density oligonucleotide microarray analyses were performed with aortic RNA from 5/6 nephrectomized (NX) and sham-operated mice. After 12 weeks, NX apoE^–/– mice had more atherosclerosis and 24 genes were differentially expressed as compared with sham apoE^–/– mice. Nine genes expressed in muscle cells displayed reduced expression (3.3- to 142-fold, P<0.05), whereas osteopontin gene expression was increased 8.7-fold (P<0.05) in NX mice. Studies of NX wild-type mice suggested that the changes in NX apoE^–/– mice were dependent on hypercholesterolemia. Nevertheless, lesioned versus nonlesioned areas of aortas from nonuremic apoE^–/– mice with classical atherosclerosis displayed less pronounced reductions in expression of the muscle cell related genes than seen in NX apoE^–/– mice even though the osteopontin gene expression was increased &15-fold. Electron microscopy showed more vacuolized and necrotic smooth muscle cells within the media underneath both nonlesioned and lesioned intima in NX than in sham apoE^–/– mice.

Conclusion— The results suggest that uremic vasculopathy in apoE^–/– mice, in addition to intimal atherosclerosis, is characterized by a uremia-specific medial smooth muscle cell degeneration, which appears to be accentuated by hypercholesterolemia.

To compare the molecular pathophysiology of classical and uremic atherosclerosis, we used high-density oligonucleotide microarray analysis to assess gene expression patterns in aortas from 5/6 nephrectomized and sham-operated apolipoprotein E-deficient mice. The results reveal that uremic vasculopathy, in addition to intimal atherosclerosis, is characterized by specific medial smooth muscle cell degeneration.

Key Words: renal failure • uremia • atherosclerosis • vascular smooth muscle cells • apolipoprotein E–deficient mice

This article has been cited by other articles:

				K. Amann Media Calcification and Intima Calcification Are Distinct Entities in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1599 - 1605. [Abstract] [Full Text] [PDF]

				X. Wu, R. Guo, Y. Wang, and P. N. Cunningham The role of ICAM-1 in endotoxin-induced acute renal failure Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1262 - F1271. [Abstract] [Full Text] [PDF]

				C. A. Bang, S. Bro, E. D. Bartels, T. X. Pedersen, and L. B. Nielsen Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1325 - F1331. [Abstract] [Full Text] [PDF]