Abstract: Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress over years to produce a weakened aorta with increased susceptibility for rupture, and currently, there are no pharmacological treatments available to slow disease progression. AAA development has been characterized by increased expression of cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation reduces AAA incidence in a mouse model of the disease. The current study determined the effectiveness of COX-2 inhibition on AAA progression when treatment was begun after initiation of the disease. COX-2 inhibitor treatment with celecoxib was initiated after angiotensin II–induced AAA formation in a strain of nonhyperlipidemic mice that we have previously identified as highly susceptible to AAA development. When analyzed at different time points during progression of the disease, celecoxib treatment significantly reduced the incidence and severity of AAAs. The celecoxib treatment also protected the mice from aortic rupture and death. The aneurysmal lesion displayed an altered smooth muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with increased expression of differentiated SMC markers and reduced dedifferentiation marker expression during AAA progression. Maintenance of a differentiated SMC phenotype is associated with the effectiveness of COX-2 inhibition for limiting AAA progression in nonhyperlipidemic mice.
*Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Canada
†Policy & Program Analysis Branch, Office of the Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
‡Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY.
Reprints: Charles D. Loftin, PhD, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Bio/Pharm Complex, Rm. 347, 789 South Limestone St, Lexington, KY 40536-0596 (e-mail: firstname.lastname@example.org).
Supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (HL083122).
The authors have no conflicts of interest to disclose.
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Received July 11, 2012
Accepted August 23, 2012