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

BACKGROUND: 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. METHODS: 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 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(2)) of glomeruli were measured using histology. RESULTS: 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 μm(2)) and number (24.8 ± 4.5) increased in apoE(-/-)/LDL(-/- )double knockout mice compared to controls (3533 ± 398 μm(2); 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. CONCLUSION: The reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE(-/-)/LDL(-/- )double knockout mouse model.