Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1

N. Grosser, K. Erdmann, A. Hemmerle, G. Berndt, U. Hinkelmann, G. Smith, H. Schröder

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Cholesterol-independent, pleiotropic actions of HMG-CoA reductase inhibitors (statins) lead to anti-inflammatory and antioxidant actions by as yet unidentified mechanisms. This study explores the role of heme oxygenase-1 (HO-1) as target and potential mediator of rosuvastatin. In cultured human endothelial cells (ECV 304), rosuvastatin increased HO-1 mRNA and protein levels in a concentration-dependent fashion. HO-1 induction by rosuvastatin remained unaffected by mevalonate and N-nitro-l-arginine-methylester, showing that isoprenoid- and NO-dependent pathways were not involved. Pretreatment of endothelial cells with rosuvastatin reduced NADPH-dependent production of oxygen radicals. The HO-1 metabolite bilirubin, when added exogenously to the cells, virtually abolished NADPH-dependent oxidative stress. Rosuvastatin-induced inhibition of free radical formation was rescued in the presence of the HO inhibitor, tin protoporphyrin-IX. Our results demonstrate that HO-1 is a target site and antioxidant mediator of rosuvastatin in endothelial cells. This novel pathway may contribute to and partially explain the pleiotropic antiatherogenic actions of rosuvastatin.

Original languageEnglish (US)
Pages (from-to)871-876
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number3
DOIs
StatePublished - Dec 17 2004

Keywords

  • Antioxidant
  • Bilirubin
  • Cytoprotection
  • Endothelial cells
  • Free radicals
  • Gene expression
  • HMG-CoA reductase inhibitor
  • Heme oxygenase
  • Pleiotropic action
  • Rosuvastatin

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