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  • Title: Aspirin and other cyclooxygenase inhibitors: new therapeutic insights.
    Author: Wu KK.
    Journal: Semin Vasc Med; 2003 May; 3(2):107-12. PubMed ID: 15199473.
    Abstract:
    Aspirin acetylates serine-530 of cyclooxygenase-1 (COX-1), thereby blocking thromboxane A (2) synthesis in platelets and reducing platelet aggregation. This mechanism of action accounts for the effect of aspirin on prevention of coronary artery and cerebrovascular thrombosis. Aspirin is less effective in inhibiting COX-2 activity, whereas celecoxib and rofecoxib selectively inhibit COX-2 activity as they contain a side chain to anchor to the side pocket of COX-2 substrate channel. Aspirin and salicylate at therapeutic concentrations inhibit COX-2 protein expression through interference with binding of CCAAT/enhancer binding protein beta (C/EBPbeta) to its cognate site on COX-2 promoter/enhancer. Expression of other genes, such as inducible nitric oxide synthase and interleukin-4, may be inhibited by aspirin and salicylate by a C/EBP-dependent mechanism. Aspirin at suprapharmacological concentrations inhibits NF-kappaB-mediated gene transcription and protects tissue from injury. These recent studies provide new insight into the pharmacological actions of aspirin and salicylate preparations and implicate C/EBPbeta as a potential target for therapy of inflammation and tissue injury.
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