Nephrol Dial Transplant (2004) 19: 566-573
Nephrol Dial Transplant Vol. 19 No. 3 (c) ERA-EDTA 2004; all rights reserved
Original Article
No aggravation of renal injury in apolipoprotein E knockout mice (ApoE–/–) after subtotal nephrectomy
1Department of Pathology and 2Department of Internal Medicine, University of Heidelberg, Heidelberg, 3Department of Pathology, 4Department of Oral and Maxillofacial Surgery and 5Department of Internal Medicine IV, University of Erlangen-Nürnberg, Erlangen and 6Department of Vegetative Physiology and Pathophysiology, UKE, Hamburg Germany
Correspondence and offprint requests to: Dr Kerstin Amann, Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstraße 8–10, D-91054 Erlangen, Germany. Email: kerstin.amann{at}patho.imed.uni-erlangen.de
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
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