Silencing of Bcl-2 gene expression by siRNA transfection inhibits the protective effect of fluvastatin against cell apoptosis in human aortic endothelial cells

Objective To study the protective effect of fluvastatin, one of the HMG-CoA reductase inhibitors (statins), against oxygen radical-induced oxidative damages in human aortic endothelial cell, and the role of Bcl-2 in this protection. Methods Human aortic endothelial cells with or without Bcl-2 siRNA transfection were subjected to 1-100 nM of fluvastatin and 100 |ìhydrogen peroxide for 24 hours. Bcl-2 mRNA and protein expression were measured by Taqman quantitative PCR and Western blotting. Cell apoptosis was measured by normal and fluorescent microscopy and Cell Death Detection ELISA. Results In the Bcl-2-expressed cells, fluvastatin significantly reversed hydrogen peroxide-induced microscopic apoptosis and apoptotic DNA fragmentation, which were accompanied by a markedly upregulation of Bcl-2 expression by fluvastatin. However, the endothelial protection by fluvastatin was completely lost in Bcl-2 siRNA transfected cells. Conclusion Fluvastatin protects human endothelial cells against oxygen radical-induced cell apoptosis in vitro, and this protection seemed to be mediated in a Bcl-2 dependent pathway.