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-kappaB (NF-kappaB) signal transduction is known to play a key role in the expression of these proatherogenic entities including tumor necrosis factor-alpha (TNF-alpha). Much data suggest that statin possess a potential anti-inflammatory effect. However, the effects of statin on the expression of TNF-alpha and activation of NF-kappaB 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 (5-100 microg/ml) for 0, 2, 4, 8, 16, 24, and 48 h. Also 10 micromol/l of fluvastatin was pre-incubated for 2 h with cells in the presence of CRP. The activity of transcription factor NF-kappaB was evaluated by electrophoretic mobility shift assay (EMSA). Measurements of TNF-alpha were performed from supernatants of cultured medium in duplicate, using commercial assay kits.
Results: CRP increased the release of TNF-alpha rapidly as a dose-and time-dependent manner. Induction of TNF-alpha was detected at 5 microg/ml and reached a maximum at 100 microg/ml of CRP. The CRP also significantly induces the activation of NF-kappaB in endothelial cells, and those effects were apparently inhibited by 10 micromol/l of fluvastatin, but not complete.
Conclusions: CRP stimulation result in induction of TNF-alpha and activation of NF-kappaB, 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.