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

PMID: 20727187 (view PubMed database entry)
DOI: 10.1186/1471-2369-11-18 (read at publisher's website )
PMCID: PMC2931481 (free full text version available)

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Alexander C Langheinrich, Marian Kampschulte, Franziska Scheiter, Christian Dierkes, Philip Stieger, Rainer M Bohle, Wolfgang Weidner,

<h4>Background</h4>The apoE-/-/LDL-/- 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.<h4>Methods</h4>Kidneys from apoE-/-/LDL-/- 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 mum cubic voxels) and Nano-CT (900 nm cubic voxels). We quantitated the total vascular volume using micro-CT. Number and cross-sectional area (microm2) of glomeruli were measured using histology.<h4>Results</h4>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-/-/LDL-/- double knockout mice, predominantly involved are plasma cells and leucocytes. Glomeruli cross-sectional area (9959 +/- 1083 microm2) and number (24.8 +/- 4.5) increased in apoE-/-/LDL-/- double knockout mice compared to controls (3533 +/- 398 microm2; 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.<h4>Conclusion</h4>The reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE-/-/LDL-/- double knockout mouse model.

BMC Nephrol (BMC nephrology)
[2010, 11:18]

Cited: 10 times

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