Abstract
BackgroundThe 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.MethodsKidneys 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 (μm2) of glomeruli were measured using histology.ResultsAt 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 μm2) and number (24.8 ± 4.5) increased in apoE-/-/LDL-/- double knockout mice compared to controls (3533 ± 398 μm2; 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.ConclusionThe reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE-/-/LDL-/- double knockout mouse model.
Highlights
The apoE-/-/LDL-/- double knockout mice are bearing considerable structural homology to human atherosclerosis
In that study we reported that the spatial location and magnitude of Vasa vasorum density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions and identified as an independent correlate to different categories of advanced lesion types
The present study demonstrates advanced atherosclerotic lesions in the renal artery and peri-vascular inflammation in kidneys of apoE-/-/LDL-/- double knockout mice at the age of 80 weeks
Summary
The apoE-/-/LDL-/- double knockout mice are bearing considerable structural homology to human atherosclerosis. This study is a continuation of our characterization of advanced atherosclerotic lesions in aortas of male apoE-/-/LDL-/- double knockout mice [13]. In that study we reported that the spatial location and magnitude of Vasa vasorum density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions and identified as an independent correlate to different categories of advanced lesion types. Inflammation in this mouse model has been shown in various organs, including the lung, heart and aorta [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
