title: Cyclooxygenase-2 and inflammation in atherosclerosis.
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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. macrae.linton@vanderbilt.edu
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D014657:Vasculitis / Q000209:etiology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases