Format

Send to:

Choose Destination
See comment in PubMed Commons below
Circulation. 2005 Apr 5;111(13):1685-9. Epub 2005 Mar 28.

Celecoxib decreases endothelial tissue factor expression through inhibition of c-Jun terminal NH2 kinase phosphorylation.

Author information

  • 1Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland.

Abstract

BACKGROUND:

Despite potential antiinflammatory properties, the use of selective cyclooxygenase-2 inhibitors (coxibs) in patients with cardiovascular diseases has been questioned because of a possibly increased thrombotic risk. Tissue factor (TF), a key protein for initiation of coagulation, has been implicated in the pathogenesis of atherosclerosis and thrombosis. Hence, we examined the effect of different coxibs on TF expression.

METHODS AND RESULTS:

Celecoxib (10(-5) mol/L), but not rofecoxib (10(-7) to 10(-5) mol/L) or the experimental coxib NS-398 (10(-7) to 10(-5) mol/L), decreased tumor necrosis factor-alpha-induced TF expression and activity in human aortic endothelial cells. Celecoxib (10(-5) mol/L) reduced activation of c-jun terminal NH2 kinase (JNK), whereas it did not affect p38 mitogen-activated protein (MAP) kinase or p44/42 MAP kinase; in contrast, JNK activation was not affected by rofecoxib (10(-5) mol/L) or NS-398 (10(-5) mol/L). TF expression was reduced in a concentration-dependent manner by pretreatment with SP600125 (10(-7) to 10(-6) mol/L), a specific inhibitor of JNK, which confirms that JNK regulates tumor necrosis factor-alpha-induced TF expression.

CONCLUSIONS:

Celecoxib reduced TF expression and activity in human aortic endothelial cells. Because neither rofecoxib nor the experimental coxib NS-398 affected TF expression, this effect occurs independently of COX-2 inhibition; it is rather mediated through inhibition of JNK phosphorylation. These data indicate a distinct heterogeneity within this class of drugs, which may be clinically relevant, especially for patients with atherosclerotic vascular diseases.

PMID:
15795326
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk