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

Article

关键词: SELECTIVE CYCLOOXYGENASE-2 INHIBITORS;    NONSTEROIDAL ANTIINFLAMMATORY DRUGS;    CORONARY ATHEROSCLEROTIC PLAQUES;    ACUTE MYOCARDIAL-INFARCTION;    PERIPHERAL ARTERY-DISEASE;    FACTOR PATHWAY INHIBITOR;    CARDIOVASCULAR EVENTS;    UNSTABLE ANGINA;    CELLS;    RISK;   

DOI  :  10.1161/01.CIR.0000160358.63804.C9

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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