Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice

Michael E. Burleigh, Vladimir R. Babaev, Mayur B. Patel, Brenda C. Crews, Rory P. Remmel, Jason D. Morrow, John A. Oates, Lawrence J. Marnett, Sergio Fazio, MacRae F. Linton

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Non-selective inhibition of cyclooxygenase (COX) has been reported to reduce atherosclerosis in both rabbit and murine models. In contrast, selective inhibition of COX-2 has been shown to suppress early atherosclerosis in LDL-receptor null mice but not more advanced lesions in apoE deficient (apoE-/-) mice. We investigated the efficacy of the novel COX inhibitor indomethacin phenethylamide (INDO-PA) on the development of different stages of atherosclerotic lesion formation in female apoE-/- mice. INDO-PA, which is highly selective for COX-2 in vitro, reduced platelet thromboxane production by 61% in vivo, indicating partial inhibition of COX-1 in vivo. Treatment of female apoE-/- mice with 5 mg/kg INDO-PA significantly reduced early to intermediate aortic atherosclerotic lesion formation (44 and 53%, respectively) in both the aortic sinus and aorta en face compared to controls. Interestingly, there was no difference in the extent of atherosclerosis in the proximal aorta in apoE-/- mice treated from 11 to 21 weeks of age with INDO-PA, yet there was a striking (76%) reduction in lesion size by en face analysis in these mice. These studies demonstrate the ability of non-selective COX inhibition with INDO-PA to reduce early to intermediate atherosclerotic lesion formation in apoE-/- mice, supporting a role for anti-inflammatory approaches in the prevention of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)334-342
Number of pages9
JournalBiochemical Pharmacology
Volume70
Issue number3
DOIs
Publication statusPublished - Aug 1 2005
Externally publishedYes

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Keywords

  • Aorta
  • ApoE mice
  • Atherosclerosis
  • COX inhibition
  • Cyclooxygenase
  • Prostaglandins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Burleigh, M. E., Babaev, V. R., Patel, M. B., Crews, B. C., Remmel, R. P., Morrow, J. D., ... Linton, M. F. (2005). Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice. Biochemical Pharmacology, 70(3), 334-342. https://doi.org/10.1016/j.bcp.2005.04.044