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 Citations (Scopus)

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
StatePublished - Aug 1 2005

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Apolipoproteins E
Prostaglandin-Endoperoxide Synthases
Atherosclerosis
Cyclooxygenase 2
Aorta
Cyclooxygenase 1
Cyclooxygenase Inhibitors
LDL Receptors
Thromboxanes
Platelets
Sinus of Valsalva
Anti-Inflammatory Agents
indomethacin phenethylamide
Blood Platelets
Rabbits

Keywords

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

Cite this

Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice. / Burleigh, Michael E.; Babaev, Vladimir R.; Patel, Mayur B.; Crews, Brenda C.; Remmel, Rory P; Morrow, Jason D.; Oates, John A.; Marnett, Lawrence J.; Fazio, Sergio; Linton, MacRae F.

In: Biochemical Pharmacology, Vol. 70, No. 3, 01.08.2005, p. 334-342.

Research output: Contribution to journalArticle

Burleigh, ME, Babaev, VR, Patel, MB, Crews, BC, Remmel, RP, Morrow, JD, Oates, JA, Marnett, LJ, Fazio, S & Linton, MF 2005, 'Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice', Biochemical Pharmacology, vol. 70, no. 3, pp. 334-342. https://doi.org/10.1016/j.bcp.2005.04.044
Burleigh, Michael E. ; Babaev, Vladimir R. ; Patel, Mayur B. ; Crews, Brenda C. ; Remmel, Rory P ; Morrow, Jason D. ; Oates, John A. ; Marnett, Lawrence J. ; Fazio, Sergio ; Linton, MacRae F. / Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice. In: Biochemical Pharmacology. 2005 ; Vol. 70, No. 3. pp. 334-342.
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