Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 13 P150

Diabetes, metabolism and cardiovascular

Bcl-2 upregulation mediates the protective effect of fluvastatin against oxidative damages in human vascular endothelial cells

Shang-Zhong Xu1, Wenwen Zhong1, Steve Lindow2, Christopher Newton1 & Stephen L Atkin1


1Postgraduate Medical Institute & Hull York Medical School, University of Hull, Hull, United Kingdom; 2Department of Obstetrics and Gynaecology, Hull Women and Children’s Hospital, Hull, United Kingdom.

Many evidences have shown that the beneficial effect of statins on the cardiovascular disease may be not only due to their cholesterol-lowering, but also may result from their non-lipid related effects, such as the improvement of endothelial function, the inhibition of smooth muscle proliferation, etc\. Here we investigated the effect of fluvastatin on H2O2-induced oxidative cell damage and the underlying mechanism in human umbilical vein endothelial cells (HUVECs).

Methods: Primary cultured HUVECs were maintained in a CO2 incubator at 37  °C. Bcl-2 siRNA and anti-Bcl2 antibody were purchased from Strategene Co. The cells were transfected with siRNA using Lipofectamine 2000. The cell proliferation, apoptosis and necrotic death were assayed with WST-1, cell death ELISA and cytotocity kits respectively, which were purchased from Roche Co. The apoptosis was also observed with trypan blue and Hoechst 33342 nuclei staining.

Results: H2O2 at 100 μM significantly induced apoptotic cell death after 24 h cell culture. Fluvastatin at low concentration (10–100 nM) prevented H2O2-induced apoptosis, as determined by the DNA fragmentation assay and cell counting with trypan blue and Hoechst 33342 staining. This protective effect was mediated by the upregulation of Bcl-2 expression probed by real-time PCR 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-senstive TRPM2 cationic channel. On the other hand, fluvastatin at moderate or high concentration (250–1000 nM) inhibited cell proliferation and induced apoptosis, but had no effect on cell necrosis.

Conclusions: Fluvastatin has a potent protective effect against H2O2-induced apoptosis. This effect is mediated by the upregulation of Bcl-2 expression. The finding provides the first evidence that Bcl-2 plays an essential role in the protective effect of fluvastatin under oxidative stress.

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