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 language | English (US) |
---|---|
Pages (from-to) | 334-342 |
Number of pages | 9 |
Journal | Biochemical Pharmacology |
Volume | 70 |
Issue number | 3 |
DOIs | |
State | Published - Aug 1 2005 |
Externally published | Yes |
Keywords
- Aorta
- ApoE mice
- Atherosclerosis
- COX inhibition
- Cyclooxygenase
- Prostaglandins
ASJC Scopus subject areas
- Biochemistry
- Pharmacology