Atherosclerosis, inflammation and lipoprotein glomerulopathy in kidneys of apoE-/-/LDL-/- double knockout mice
Open accessAbstract
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. CONCLUSION: The reduced intra-renal total vascular volume is associated with systemic atherosclerosis and glomeruli alterations in the apoE-/-/LDL-/- double knockout mouse model.
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apoE-/- and DKO mice have been reported to develop renal abnormalities that are different from those found in LPG.
“apoE Ϫ / Ϫ and DKO mice have been reported to develop renal abnormalities that are different from those found in LPG (40)(41)(42).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [42]
The Results report renal-artery atherosclerosis, perivascular inflammation, and reduced renal vascular volume in double-knockout (DKO) mice—abnormalities beyond the glomerular lipoprotein deposits used to characterize LPG. But the same Results report LPG in 41% of their glomeruli, and the Discussion says apoE-/- mice spontaneously develop LPG. The source therefore does not support a broad distinction between the mice’s renal abnormalities and LPG. (LLM, conf=0.84)
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Research works printed but not linked: 24
- Fassett RG D'Intini V Healy H Gowardman J Gan JS Sharman JE Assessment of arterial stiffness, oxidative stress and inflammation in acute kidney injury [In Process Citation] BMC Nephrol 2009 10 15 10.1186/1471-2369-10-15 19538714 PMC2702366 · DOI
- Attman PO Samuelsson O Dyslipidemia of kidney disease [In Process Citation] Curr Opin Lipidol 2009 20 293 29 10.1097/MOL.0b013e32832dd832 19512921 · DOI
- Bahous SA Blacher J Safar ME Aortic stiffness, kidney disease, and renal transplantation Curr Hypertens Rep 2009 11 98 03 10.1007/s11906-009-0019-4 19278598 · DOI
- Kastarinen H Ukkola O Kesaniemi YA Glomerular filtration rate is related to carotid intima-media thickness in middle-aged adults Nephrol Dial Transplant 2009 24 2767 2772 10.1093/ndt/gfp172 19369688 · DOI
- Schiele F Renal dysfunction and coronary disease: a high-risk combination J Nephrol 2009 22 39 45 19229817
- Zoja C Abbate M Remuzzi G Progression of chronic kidney disease: insights from animal models Curr Opin Nephrol Hypertens 2006 15 250 257 10.1097/01.mnh.0000222691.53970.83 16609291 · DOI
- Kimura M Suzuki T Hishida A A rat model of progressive chronic renal failure produced by microembolism Am J Pathol 1999 155 1371 1380 10514419 PMC1867024
- Bianchi G Ferrari P Cusi D Salardi S Guidi E Niutta E Genetic and experimental hypertension in the animal model-similarities and dissimilarities to the development of human hypertension J Cardiovasc Pharmacol 1986 8 Suppl 5 S64 S70 10.1097/00005344-198608005-00013 2427888 · DOI
- Lee HT Park SW Kim M D'Agati VD Acute kidney injury after hepatic ischemia and reperfusion injury in mice Lab Invest 2009 89 196 208 10.1038/labinvest.2008.124 19079326 PMC2632727 · DOI
- Gaillard V Jover B Casellas D Cordaillat M Atkinson J Lartaud I Renal function and structure in a rat model of arterial calcification and increased pulse pressure Am J Physiol Renal Physiol 2008 295 F1222 F1229 10.1152/ajprenal.00081.2008 18715942 · DOI
- Dixon JL Stoops JD Parker JL Laughlin MH Weisman GA Sturek M Dyslipidemia and vascular dysfunction in diabetic pigs fed an atherogenic diet Arterioscler Thromb Vasc Biol 1999 19 2981 2992 10591679
- Ishimura A Watanabe M Nakashima H Ito K Miyake K Mochizuki S Lipoprotein glomerulopathy induced by ApoE-Sendai is different from glomerular lesions in aged apoE-deficient mice Clin Exp Nephrol 2009 13 430 437 10.1007/s10157-009-0195-1 19459027 · DOI · Paper page
- Langheinrich AC Michniewicz A Sedding DG Walker G Beighley PE Rau WS Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(-/-)/low-density lipoprotein(-/-) double knockout mice Arterioscler Thromb Vasc Biol 2006 26 347 352 10.1161/01.ATV.0000196565.38679.6d 16293797 · DOI
- Langheinrich AC Michniewicz A Bohle RM Ritman EL Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE-/-/LDL-/- double knockout mice Atherosclerosis 2007 191 73 81 10.1016/j.atherosclerosis.2006.05.021 16806224 · DOI
- Chade AR Lerman A Lerman LO Kidney in early atherosclerosis Hypertension 2005 45 1042 1049 10.1161/01.HYP.0000167121.14254.a0 15897370 · DOI
- Godin DV Dahlman DM Effects of hypercholesterolemia on tissue antioxidant status in two species differing in susceptibility to atherosclerosis Res Commun Chem Pathol Pharmacol 1993 79 151 166 8451540
- Kshirsagar AV Colindres RE Systemic atherosclerosis and kidney disease Arch Intern Med 2006 166 250 10.1001/archinte.166.2.250-a 16432101 · DOI
- Magoori K Kang MJ Ito MR Kakuuchi H Ioka RX Kamataki A Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E J Biol Chem 2003 278 11331 11336 10.1074/jbc.M211987200 12509421 · DOI
- Ishibashi S Herz J Maeda N Goldstein JL Brown MS The two-receptor model of lipoprotein clearance: tests of the hypothesis in "knockout" mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins Proc Natl Acad Sci USA 1994 91 4431 4435 10.1073/pnas.91.10.4431 8183926 PMC43799 · DOI · Paper page
- Helmchen U Bohle RM Kneissler U Groene HJ Intrarenal arteries in rats with early two-kidney, one clip hypertension Hypertension 1984 6 III87 III92 6394494
- Helmchen U Kneissler U Bohle RM Reher A Groene HJ Adaptation and decompensation of intrarenal small arteries in experimental hypertension J Cardiovasc Pharmacol 1984 6 Suppl 4 S696 S705 10.1097/00005344-198406004-00017 6083413 · DOI
- Kai H Kuwahara F Tokuda K Shibata R Kusaba K Niiyama H Coexistence of hypercholesterolemia and hypertension impairs adventitial vascularization Hypertension 2002 39 455 459 10.1161/hy0202.103001 11882589 · DOI
- Hoffmann M Scharnagl H Panagiotou E Banghard W Wieland H Marz W Diminished LDL receptor and high heparin binding of apolipoprotein E2 Sendai associated with lipoprotein glomerulopathy J Am Soc Nephrol 2001 12 524 530 11181800
- Komatsu T Kanatsu K Ochi H Kita T Doi T Lipoprotein glomerulopathy with a new apolipoprotein E phenotype Am J Kidney Dis 1995 25 952 953 10.1016/0272-6386(95)90581-2 7771495 · DOI
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Tavori, H., Fan, D., Giunzioni, I., Zhu, L., Linton, M. F., Fogo, A. B., & Fazio, S. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m049874 · Cited by 10 · see citing works
- Authors
- Langheinrich, A. C., Kampschulte, M., Scheiter, F., Dierkes, C., Stieger, P., Bohle, R. M., & Weidner, W.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Saarland University (DE)
- Corresponding author
- Langheinrich, Alexander C
- Venue
- BMC Nephrology
- Published
- 2010-08-20
- Volume
- 11
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1471-2369 (ISSN-L)
- PMC
- PMC2931481
- OpenAlex
- W1975146742
- Cited by
- 15
- References
- 0
- Citations by year
- 2023: 1 · 2021: 1 · 2019: 2 · 2018: 3 · 2016: 1 · 2015: 1 · 2014: 4 · 2012: 1
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Nephrology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Universität des Saarlandes
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- atherosclerosis, lipoprotein glomerulopathy, renal artery atherosclerosis, perivascular inflammation, glomerular hypertrophy, systemic atherosclerosis
- MeSH terms
- Animals, Apolipoproteins E, Disease Models, Animal, Glomerulonephritis, Kidney Glomerulus, Leukocytes, Lipoproteins, Lipoproteins, LDL, Male, Neovascularization, Pathologic, Plasma Cells, Renal Artery, Tomography, X-Ray Computed, Vasa Vasorum, Mice, Knockout, Imaging, Three-Dimensional, Nanotechnology, Atherosclerosis, Mice
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