on March 2, 2006
Published online before print March 2, 2006, doi: 10.1161/01.ATV.0000216119.79008.ac
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Submitted on December 7, 2005
Accepted on February 17, 2006
Selective Cyclooxygenase-2 Inhibition With Celecoxib Decreases Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice
Victoria L. King *;
From the Cardiovascular Research Center (V.L.K.), Department of Medicine (V.L.K.), Department of Pharmaceutical Sciences, College of Pharmacy (D.T., J.M.G., C.D.L.), University of Kentucky, Lexington.
* To whom correspondence should be addressed. E-mail: vicky.king{at}uky.edu.
Objective--Inflammation plays an integral role in the development of abdominal aortic aneurysms (AAAs), and the expression of cyclooxygenase-2 (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 per day), or celecoxib (125 mg/kg per day), respectively. COX inhibitors were administered 1 week before angiotensin II (Ang II; 1000 ng/kg per minute) 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.
Key words: cyclooxygenase-1 • cyclooxygenase-2 • abdominal aortic aneurysms • celecoxib • prostaglandin E2
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