title: Selective cyclooxygenase-2 inhibition with celecoxib decreases angiotensin II-induced abdominal aortic aneurysm formation in mice.
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.
  
  
  RESULTS
  Eight-week-old male apolipoprotein E-deficient mice were treated with selective inhibitors of COX-1 or COX-2, SC-560 (approximately 25 mg.kg(-1).day(-1)), or celecoxib (approximately 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.
authors.affiliation: Cardiovascular Research Center, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536-0020, USA. vicky.king@uky.edu
authors.forename: Victoria L
authors.initials: VL
authors.lastname: King
authors.forename: Darshini B
authors.initials: DB
authors.lastname: Trivedi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gitlin
authors.forename: Charles D
authors.initials: CD
authors.lastname: Loftin
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000502:physiology; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D006937:Hypercholesterolemia / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D001057:Apolipoproteins E; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000804:Angiotensin II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone; D015230:Prostaglandin D2