Cyclooxygenase-2 and inflammation in atherosclerosis

MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalReview articlepeer-review

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
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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