title: Fluvastatin inhibits the expression of tumor necrosis factor-alpha and activation of nuclear factor-kappaB 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-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.
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University School of Medicine, 238 JieFang Road, Wuhan 430060, People's Republic of China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Wang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D002097:C-Reactive Protein / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000077340:Fluvastatin; D002097:C-Reactive Protein