Fluvastatin inhibits the expression of tumor necrosis factor-+A7E and activation of nuclear factor-+A7o-B in human endothelial cells stimulated by C-reactive protein

Abstract

Background Inflammation plays a critic role in atherosclerosis and C-reactive protein (CRP) may directly facilitate the development of a proinflammatory and proatheroscleroitc phenotype. The nuclear factor-+A7o-B (NF-+A7o-B) signal transduction is known to play a key role in the expression of these proatherogenic entities including tumor necrosis factor-+A7E (TNF-+A7E). Much data suggest that statin possess a potential anti-inflammatory effect. However, the effects of statin on the expression of TNF-+A7E and activation of NF-+A7o-B in endothelial cells stimulated by CRP are less studied. We determined the effects of CRP in inducing inflammatory response and the effect of fluvastatin on CRP-dependent inflammatory activation in human cultured endothelial cells. Methods Human vascular endothelial cells were cultured and stimulated by concentrations of CRP (5+IBMAkw-100 +A7w-g/ml) for 0, 2, 4, 8, 16, 24, and 48 h. Also 10 +A7w-mol/l of fluvastatin was pre-incubated for 2 h with cells in the presence of CRP. The activity of transcription factor NF-+A7o-B was evaluated by electrophoretic mobility shift assay (EMSA). Measurements of TNF-+A7E were performed from supernatants of cultured medium in duplicate, using commercial assay kits. Results CRP increased the release of TNF-+A7E rapidly as a dose-and time-dependent manner. Induction of TNF-+A7E was detected at 5 +A7w-g/ml and reached a maximum at 100 +A7w-g/ml of CRP. The CRP also significantly induces the activation of NF-+A7o-B in endothelial cells, and those effects were apparently inhibited by 10 +A7w-mol/l of fluvastatin, but not complete. Conclusions CRP stimulation result in induction of TNF-+A7E and activation of NF-+A7o-B, and this effect could be significantly inhibited by fluvastatin, suggesting that CRP may play a direct role in atherogenesis by activating endothelial cells, and statins inhibit this response, which may provide an insight into the mechanisms of anti-inflammatory or anti-atherosclerotic actions of statins.