TY - JOUR
T1 - Cyclooxygenase-2 and inflammation in atherosclerosis
AU - Linton, MacRae F.
AU - Fazio, Sergio
N1 - Funding Information:
The authors are supported by National Institutes of Health grants HL53989, HL58427, HL57986 and HL65405.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.coph.2003.12.003
DO - 10.1016/j.coph.2003.12.003
M3 - Review article
C2 - 15063354
AN - SCOPUS:1842453964
SN - 1471-4892
VL - 4
SP - 116
EP - 123
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 2
ER -