Cyclooxygenase-2 and inflammation in atherosclerosis

MacRae F. Linton, Sergio Fazio

    Research output: Contribution to journalReview article

    112 Scopus citations

    Abstract

    By regulating the production of eicosanoids, cyclooxygenase (COX) modulates processes contributing to atherosclerosis and thrombosis, including platelet aggregation and the local inflammatory response. COX-2, a key mediator of inflammation, is upregulated in activated monocyte/macrophages, suggesting that COX-2 inhibition might reduce atherogenesis through its anti-inflammatory effects. In mouse models, selective inhibition of COX-2 or its deletion in macrophages protects against early atherosclerosis. The discovery that macrophage COX-2 is downregulated by oxidized low-density lipoprotein and liver X receptors indicates coordinated and reciprocal control of cholesterol homeostasis and inflammatory pathways. Thus, the impact of macrophage COX-2 expression on atherogenesis might be attenuated in advanced lesions. Concerns have been raised that inhibition of COX-2 might promote thrombotic cardiovascular events by disturbing the balance between platelet thromboxane A2 and endothelial prostacyclin. However, meta-analyses of randomized trials have failed to show excess of cardiovascular events among patients on COX-2 inhibitors. Prospective randomized evaluation of the effects of selective COX-2 inhibitors on cardiovascular events is warranted.

    Original languageEnglish (US)
    Pages (from-to)116-123
    Number of pages8
    JournalCurrent Opinion in Pharmacology
    Volume4
    Issue number2
    DOIs
    StatePublished - Apr 1 2004

    ASJC Scopus subject areas

    • Pharmacology
    • Drug Discovery

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