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 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.


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 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.


CONCLUSIONS
The reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE-/-/LDL-/- double knockout mouse model.
Langheinrich
Alexander C
AC
Department of Radiology, Justus-Liebig University Giessen, Giessen, Germany. alexander.langheinrich@radiol.med.uni-giessen.de
Kampschulte
Marian
M
Scheiter
Franziska
F
Dierkes
Christian
C
Stieger
Philip
P
Bohle
Rainer M
RM
Weidner
Wolfgang
W
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D021621:Imaging, Three-Dimensional; D007678:Kidney Glomerulus / Q000648:ultrastructure; D007962:Leukocytes / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036103:Nanotechnology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D012077:Renal Artery / Q000473:pathology*; D014057:Tomography, X-Ray Computed / Q000379:methods; D014651:Vasa Vasorum / Q000473:pathology
D001057:Apolipoproteins E; D008074:Lipoproteins; D008077:Lipoproteins, LDL