@article { , title = {Fluvastatin reduces oxidative damage in human vascular endothelial cells by upregulating Bcl-2}, 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.}, doi = {10.1111/j.1538-7836.2008.02913.x}, eissn = {1538-7836}, issn = {1538-7933}, issue = {4}, journal = {Journal Of Thrombosis And Haemostasis}, pages = {692-700}, publicationstatus = {Published}, publisher = {Wiley}, url = {https://hull-repository.worktribe.com/output/461231}, volume = {6}, keyword = {Health and Health Inequalities, Apoptosis, Bcl‐2, Cell proliferation, Endothelial cells, Fluvastatin, Hydrogen peroxide, TRPM2}, year = {2008}, author = {Xu, S. Z. and Zhong, W. and Watson, N. M. and Dickerson, E. and Wake, J. D. and Lindow, S. W. and Newton, C. J. and Atkin, S. L.} }