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.