Selective cyclooxygenase-2 inhibition with celecoxib decreases angiotensin II -induced abdominal aortic aneurysm formation in mice

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 ( approximate to 25 mg . kg(-1) . day(-1)), or celecoxib (approximate to 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.