Abstract
Objective - Inflammation plays an integral role in the development of abdominal aortic aneurysms (AAAs), and the expression of cyclooxygenase (COX)-2 is increased in aneurysmal tissue compared with normal aorta. Nonsteroidal anti-inflammatory drugs, which inhibit the activity of COX-1 and COX-2, decrease AAA expansion in humans and animal models of the disease. In the current study, we investigated the effectiveness of selective inhibition of COX-1 or COX-2 in attenuating AAA formation. Methods and Results - Eight-week-old male apolipoprotein E-deficient mice were treated with selective inhibitors of COX-1 or COX-2, SC-560 (≈25 mg·kg-1·day-1), or celecoxib (≈125 mg·kg-1·day-1), respectively. COX inhibitors were administered 1 week before angiotensin II (Ang II; 1000 ng·kg-1·min-1) or saline infusion and throughout the time course of the experiment. COX-1 inhibition had no effect on incidence (control: 90% [9:10] versus SC-560: 89% [8:9]) or severity of Ang II-induced AAA formation. In contrast, celecoxib decreased the incidence (control: 74% [22:30] versus celecoxib: 11% [2:19]; P<0.001) and severity (P=0.001) of AAA formation. Celecoxib also decreased the incidence and severity of AAAs in nonhyperlipidemic mice. Conclusions - COX-2-derived prostanoids play a fundamental role in the development of Ang II-induced AAAs in both hyperlipidemic and nonhyperlipidemic mice.
Original language | English |
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Pages (from-to) | 1137-1143 |
Number of pages | 7 |
Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
Volume | 26 |
Issue number | 5 |
DOIs | |
State | Published - May 2006 |
Keywords
- Abdominal aortic aneurysms
- Celecoxib
- Cyclooxygenase-1
- Cyclooxygenase-2
- Prostaglandin E
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine