Journal Article

No aggravation of renal injury in apolipoprotein E knockout mice (ApoE<sup>–/–</sup>) after subtotal nephrectomy

Moriz Buzello, Christian Stefan Haas, Frank Hauptmann, Marie Luise Gross, Jörg Faulhaber, Stefan Schultze-Mosgau, Heimo Ehmke, Eberhard Ritz and Kerstin Amann

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 3, pages 566-573
Published in print March 2004 | ISSN: 0931-0509
Published online March 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg578
No aggravation of renal injury in apolipoprotein E knockout mice (ApoE–/–) after subtotal nephrectomy

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Background. There is substantial experimental evidence that various forms of dyslipidaemia aggravate the course of renal failure and that reversal of dyslipidaemia ameliorates progression of renal failure. The apolipoprotein E knockout mouse (ApoE–/–) is an established model of accelerated atherogenesis. We investigated whether the course of renal disease after uninephrectomy (UNX) and subtotal nephrectomy (SNX) is altered in ApoE–/– mice compared with their genetic controls.

Methods. Ten-week-old, male ApoE–/– mice (body weight 25±2 g) were subjected either to sham operation (sham), UNX or SNX. C57BL/6 sham, UNX and SNX mice served as controls (body weight 26±3 g). The food intake of ApoE–/– and C57BL/6 mice was kept identical by a pair-feeding protocol. After 12 weeks, mean arterial blood pressure and heart rate were measured in awake resting mice, the kidneys were perfusion fixed and analysed using quantitative histological methods, immunohistochemistry and RT–PCR.

Results. At baseline, the sham ApoE–/– mice had significantly higher (P<0.05) serum cholesterol and triglycerides than the controls. In parallel, mean arterial blood pressure was significantly elevated in sham ApoE–/– mice compared with controls (137±15 vs 116±4 mmHg; P<0.05). In the sham groups, the glomerulosclerosis index was significantly higher in the ApoE–/– mice (1.05±0.14 vs 0.57±0.07; P<0.05), whereas the tubulointerstitial damage score was comparable (0.06±0.04 vs 0.04±0.02; n.s.). After SNX there was a significant increase in glomerulosclerosis index, but no difference could be detected between ApoE–/– and controls (1.75±0.16 vs 1.61±0.01, n.s.). The same was true for the tubulointerstitial damage index.

Conclusions. Despite some glomerulosclerosis and elevated mean arterial blood pressure at baseline, no acceleration of progression of renal disease was found in this genetic model of hyperlipoproteinaemia. This observation suggests that despite the known spontaneous histological changes in untouched kidneys, however, the presence of hyperlipidaemia in the ApoE–/– mouse does not cause more severe progression in the present models of moderate renal disease.

Keywords: ApoE–/– knockout mouse; dyslipidaemia; glomerulosclerosis; progression of renal failure; subtotal nephrectomy

Journal Article.  4800 words.  Illustrated.

Subjects: Nephrology

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