Document Detail


Fluvastatin inhibits the expression of tumor necrosis factor-alpha and activation of nuclear factor-kappaB in human endothelial cells stimulated by C-reactive protein.
MedLine Citation:
PMID:  15698590     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Hai-Rong Wang; Jian-Jun Li; Cong-Xin Huang; Hong Jiang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinica chimica acta; international journal of clinical chemistry     Volume:  353     ISSN:  0009-8981     ISO Abbreviation:  Clin. Chim. Acta     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-08     Completed Date:  2005-04-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1302422     Medline TA:  Clin Chim Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  53-60     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Renmin Hospital, Wuhan University School of Medicine, 238 JieFang Road, Wuhan 430060, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
C-Reactive Protein / physiology*
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects*
Fatty Acids, Monounsaturated / pharmacology*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Indoles / pharmacology*
NF-kappa B / metabolism*
Tumor Necrosis Factor-alpha / metabolism*
Chemical
Reg. No./Substance:
0/Fatty Acids, Monounsaturated; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Indoles; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha; 9007-41-4/C-Reactive Protein; 93957-54-1/fluvastatin

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