Fluvastatin reduces oxidative damage in human vascular endothelial cells by upregulating Bcl-2

Shang Zhong Xu, W. Zhong, N. M. Watson, E. Dickerson, J. D. Wake, S. W. Lindow, C. J. Newton, Stephen Atkin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been widely used in clinical practise and their efficacy in reducing cardiovascular risk has been well described. Objectives: Toinvestigate the effect of low doses of fluvastatin (nanomolar) on H2O2-induced cell damage and the underlying mechanism. Methods and results: Primary cultures of human umbilical vein endothelial cells were used, and the effects of fluvastatin on H2O2-induced apoptosis, necrosis, and proliferation were observed. H2O2 at a concentration of 100 μm significantly induced apoptotic cell death after 24-h cell culture. Fluvastatin at low concentrations (10-100 nm) prevented H2O2-induced apoptosis, as determined by a DNA fragmentation assay and by cell counting with trypan blue and Hoechst 33342 nuclei staining. The protective effect of fluvastatin was mediated by the upregulation of Bcl-2 expression as probed by real-time polymerase chain reaction and Western blotting. Using siRNA to knock down the expression of Bcl-2, the protective effect of fluvastatin was abolished. Fluvastatin had no direct effect on the H2 O2-sensitive TRPM2 calcium channel. Conclusions: These results suggest that fluvastatin has a potent protective effect against H2O2-induced apoptosis via upregulation of Bcl-2 expression. The findings provide a new insight into the mechanism by which fluvastatin is able to modulate the influence of oxidative stress on vascular endothelial cells.

Original languageEnglish
Pages (from-to)692-700
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

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Keywords

  • Apoptosis
  • Bcl-2
  • Cell proliferation
  • Endothelial cells
  • Fluvastatin
  • Hydrogen peroxide
  • TRPM2

ASJC Scopus subject areas

  • Hematology

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