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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1137.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Selective Cyclooxygenase-2 Inhibition With Celecoxib Decreases Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice

Victoria L. King; Darshini B. Trivedi; Jonathan M. Gitlin; Charles D. Loftin

From the Cardiovascular Research Center (V.L.K.), Department of Internal Medicine (V.L.K.), Department of Pharmaceutical Sciences, College of Pharmacy (D.B.T., J.M.G., C.D.L.), University of Kentucky, Lexington.

Correspondence to Victoria L. King, Cardiovascular Research Center, Wethington Building, Room 562, University of Kentucky, Lexington, KY 40536-0020. E-mail vicky.king{at}uky.edu; or Charles D. Loftin, Department of Pharmaceutical Sciences, 725 Rose St, Room 414, University of Kentucky, Lexington, KY 40536-0082. E-mail cdloft2@uky.edu

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.

COX-2 expression is increased in aneurysmal tissue, and nonselective inhibition of COXs decreases AAA expansion. The present study demonstrates that selective COX-1 inhibition does not alter Ang II-induced AAA formation. In contrast, selective COX-2 inhibition with celecoxib attenuates Ang II-induced AAA formation in both nonhyperlipidemic and hyperlipidemic mice.

Key Words: cyclooxygenase-1 • cyclooxygenase-2 • abdominal aortic aneurysms • celecoxib • prostaglandin E₂

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