Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia

Stephanie H. Wilson, Alejandro R. Chade, Ariel Feldstein, Tatsuya Sawamura, Claudio Napoli, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Background. Hypercholesterolaemia (HC), an independent risk factor for renal injury, is associated with formation of oxidized low-density-lipoprotein (ox-LDL), increased oxidative-stress and renal inflammation. HMG-CoA-reductase inhibitors are commonly used in HC, but their effects on renal haemodynamics and function in HC are poorly understood. Methods. Pigs were studied after a 12-week normal diet, a 2% high-cholesterol diet (HC) or an HC diet supplemented with simvastatin (HC+simvastatin, 80 mg/day) (n = 6-8 each group). Renal haemodynamics and function were quantified in vivo with electron-beam computed tomography (EBCT). Shock-frozen renal tissue was subsequently studied using immunohistochemistry. Results. LDL cholesterol was similarly increased in HC and HC+simvastatin. Simvastatin-treated animals showed increased expression of endothelial nitric-oxide-synthase (eNOS), and decreased expression of the ox-LDL receptor LOX-1 in renal endothelial cells. Simvastatin also decreased tubular immunoreactivity of inducible-NOS, nitrotyrosine, nuclear-factor-κB, and tubuloglomerular trichrome staining. These were associated with a significant increase in cortical (6.1 ± 0.1 vs 5.0 ± 0.3 and 5.0 ± 0.1 ml/min/cc, respectively, P < 0.001) and medullary perfusion in HC + simvastatin compared to normal and HC. Conclusions. Simvastatin attenuated the inflammatory and pro-oxidative environment as well as fibrosis in kidneys in pigs with diet-induced HC, in association with enhanced renal perfusion. These cholesterol-lowering-independent changes imply novel renoprotective effects of statins in the setting of HC and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)703-709
Number of pages7
JournalNephrology Dialysis Transplantation
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2003

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Keywords

  • HMG-CoA reductase inhibitors
  • Hyper-cholesterolaemia
  • Kidney

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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