Atherosclerosis, inflammation and lipoprotein glomerulopathy in kidneys of apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice

<p>Abstract</p> <p>Background</p> <p>The apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice are bearing considerable structural homology to human atherosclerosis. We hypothesized, that advanced lesion formation in the renal artery is assoc...

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Bibliographic Details
Main Authors: Langheinrich Alexander C, Kampschulte Marian, Scheiter Franziska, Dierkes Christian, Stieger Philip, Bohle Rainer M, Weidner Wolfgang
Format: Article
Language:English
Published: BMC 2010-08-01
Series:BMC Nephrology
Online Access:http://www.biomedcentral.com/1471-2369/11/18
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Summary:<p>Abstract</p> <p>Background</p> <p>The apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice are bearing considerable structural homology to human atherosclerosis. We hypothesized, that advanced lesion formation in the renal artery is associated with kidney alterations in these mice.</p> <p>Methods</p> <p>Kidneys from apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice at the age of 80 weeks (n = 6) and C57/BL control mice (n = 5) were infused with Microfil, harvested and scanned with micro-CT (12 μm cubic voxels) and Nano-CT (900 nm cubic voxels). We quantitated the total vascular volume using micro-CT. Number and cross-sectional area (μm<sup>2</sup>) of glomeruli were measured using histology.</p> <p>Results</p> <p>At the age of 80 weeks, the renal total vascular volume fraction decreased significantly (p < 0.001) compared to controls. Moreover, the renal artery showed advanced atherosclerotic lesions with adventitial Vasa vasorum neovascularization. Perivascular inflammation was present in kidneys of apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice, predominantly involved are plasma cells and leucocytes. Glomeruli cross-sectional area (9959 ± 1083 μm<sup>2</sup>) and number (24.8 ± 4.5) increased in apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mice compared to controls (3533 ± 398 μm<sup>2</sup>; 17.6 ± 3, respectively), whereas 41% of the total number of glomeruli showed evidence for lipoprotein associated glomerulopathy (LPG). Moreover, immunohistochemistry demonstrated capillary aneurysms of the glomeruli filled with factor 8 containing emboli.</p> <p>Conclusion</p> <p>The reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE<sup>-/-</sup>/LDL<sup>-/- </sup>double knockout mouse model.</p>
ISSN:1471-2369