The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse

Giunti, Sara, Calkin, Anna C., Forbes, Josephine M., Allen, Terri J., Thomas, Merlin C., Cooper, Mark E. and Jandeleit-Dahm, Karin A. (2010) The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse. American Journal of Physiology - Renal Physiology, 299 3: F528-F535. doi:10.1152/ajprenal.00127.2010

Author Giunti, Sara
Calkin, Anna C.
Forbes, Josephine M.
Allen, Terri J.
Thomas, Merlin C.
Cooper, Mark E.
Jandeleit-Dahm, Karin A.
Title The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse
Journal name American Journal of Physiology - Renal Physiology   Check publisher's open access policy
ISSN 0363-6127
Publication date 2010-09-01
Sub-type Article (original research)
DOI 10.1152/ajprenal.00127.2010
Open Access Status
Volume 299
Issue 3
Start page F528
End page F535
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Formatted abstract
Diabetic nephropathy is a leading cause of end-stage renal disease. Statins may exert renoprotective effects independently of lipid-lowering properties. We investigated the pleiotropic effects of rosuvastatin on renal structure and function in streptozotocin diabetic apolipoprotein-E knockout (Apo-E -/-) mice, a model of progressive nephropathy in which dyslipidemia is resistant to statin treatment. These effects were compared with those observed with conventional renin-angiotensin system blockade (candesartan) or combined treatment. Nondiabetic and diabetic Apo-E-/- mice were randomized to no treatment or treatment with candesartan (2.5 mg/kg), rosuvastatin (5 mg/kg), or their combination per gavage for 20 wk. Urine and blood samples were collected for assessment of albuminuria, creatinine clearance, plasma lipids, glucose, and glycated hemoglobin. Renal sclerosis was analyzed on paraffin-embedded kidney sections stained with periodic acid-Schiff. Renal expression of collagen IV, fibronectin and advanced glycation end products (AGEs), receptor for advanced glycation and products (RAGE), NADPH oxidase 4 (NOX4), and nitrotyrosine was assessed by real-time PCR and/or immunohistochemistry. Diabetes-induced albuminuria was not affected by rosuvastatin and combination treatment but was prevented by candesartan. Diabetes resulted in increased creatinine clearance, which was not modified by the treatments. Rosuvastatin and/or candesartan prevented diabetes-associated renal extracellular matrix accumulation. Rosuvastatin reduced accumulation of AGEs and expression of RAGE, NOX4, and nitrotyrosine. In conclusion, in the diabetic Apo-E-/- mouse, rosuvastatin confers renal benefits that are independent of lipid lowering and equivalent or greater to those observed with candesartan. The combination treatment is not superior to monotherapies.
Keyword Angiotensin type 1 receptor antagonist
Experimental diabetes
Kidney disease
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
School of Medicine Publications
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