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

Xu, S. Z.; Zhong, W.; Watson, N. M.; Dickerson, E.; Wake, J. D.; Lindow, S. W.; Newton, C. J.; Atkin, S. L.

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: To investigate 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 mu M 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 H2O2-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.

Citation

Xu, S. Z., Zhong, W., Watson, N. M., Dickerson, E., Wake, J. D., Lindow, S. W., Newton, C. J., & Atkin, S. L. (2008). Fluvastatin reduces oxidative damage in human vascular endothelial cells by upregulating Bcl-2. Journal of thrombosis and haemostasis : JTH, 6(4), 692-700. https://doi.org/10.1111/j.1538-7836.2008.02913.x

• Journal Article Type: Article
• Acceptance Date: Jan 16, 2008
• Online Publication Date: Jan 22, 2008
• Publication Date: Apr 1, 2008
• Deposit Date: Nov 13, 2014
• Journal: Journal Of Thrombosis And Haemostasis
• Print ISSN: 1538-7933
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 4
• Pages: 692-700
• DOI: https://doi.org/10.1111/j.1538-7836.2008.02913.x
• Keywords: Apoptosis; Bcl‐2; Cell proliferation; Endothelial cells; Fluvastatin; Hydrogen peroxide; TRPM2
• Public URL: https://hull-repository.worktribe.com/output/461231
• Contract Date: Nov 13, 2014