Cyclooxygenase-2 and atherosclerosis

MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Cyclooxygenase regulates the production of eicosanoids, which modulate physiologic processes in the vessel wall contributing to atherosclerosis and thrombosis, including platelet aggregation, control of vascular tone, and the local inflammatory response. Cyclooxygenase-1 mediates production of platelet thromboxane A2, a potent vasoconstrictor and platelet agonist, whereas both cyclooxygenase 1 and 2 contribute to production of endothelial prostacyclin, a vasodilator that inhibits platelet activation. Concerns have been raised that cyclooxygenase-2 inhibitors may increase thrombotic cardiovascular events by disturbing the balance between platelet thromboxane A2 and endothelial prostacyclin, but this controversial issue will only be resolved by prospective clinical trials. Because cyclooxygenase-2 is upregulated in activated monocyte/macrophages, which play a key role in the pathogenesis of atherosclerosis, we have recently tested the hypothesis that pharmacological inhibition of cyclooxygenase-2 in LDL-receptor deficient mice would reduce early atherosclerosis. After 6 weeks on a Western-type diet, male LDL-receptor deficient mice treated with either rofecoxib (a selective cyclooxygenase-2 inhibitor) or indomethacin (a non-selective cyclooxygenase inhibitor) had significant reductions in atherosclerosis when compared with control mice. Also, LDL-receptor deficient mice null for macrophage cyclooxygenase-2 were generated by fetal liver cell transplantation and developed significantly less atherosclerosis than control LDL-receptor deficient mice transplanted with fetal liver cells wildtype for cyclooxygenase-2, providing genetic evidence in support of a proatherogenic role for macrophage cyclooxygenase-2 expression. These results support the potential of antiinflammatory approaches for the prevention of atherosclerosis and identify cyclooxygenase-2 as a target for intervention.

Original languageEnglish (US)
Pages (from-to)497-504
Number of pages8
JournalCurrent Opinion in Lipidology
Volume13
Issue number5
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Atherosclerosis
Platelets
LDL Receptors
Macrophages
Cyclooxygenase 1
Thromboxane A2
Blood Platelets
Cyclooxygenase 2 Inhibitors
Epoprostenol
Liver
Cyclooxygenase Inhibitors
Eicosanoids
Cell Transplantation
Platelet Activation
Vasoconstrictor Agents
Prostaglandin-Endoperoxide Synthases
Nutrition
Vasodilator Agents
Platelet Aggregation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cyclooxygenase-2 and atherosclerosis. / Linton, MacRae F.; Fazio, Sergio.

In: Current Opinion in Lipidology, Vol. 13, No. 5, 10.2002, p. 497-504.

Research output: Contribution to journalArticle

Linton, MacRae F. ; Fazio, Sergio. / Cyclooxygenase-2 and atherosclerosis. In: Current Opinion in Lipidology. 2002 ; Vol. 13, No. 5. pp. 497-504.
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