title: Cyclooxygenase-2 inhibition attenuates abdominal aortic aneurysm progression in hyperlipidemic mice.
abstract: Abdominal aortic aneurysms (AAAs) are a chronic inflammatory disease that increase the risk of life-threatening aortic rupture. In humans, AAAs have been characterized by increased expression of cyclooxygenase-2 and the inactivation of COX-2 prior to disease initiation reduces AAA incidence in a mouse model of the disease. The current study examined the effectiveness of selective cyclooxygenase-2 (COX-2) inhibition on reducing AAA progression when administered after the initiation of AAA formation. AAAs were induced in hyperlipidemic apolipoprotein E-deficient mice by chronic angiotensin II (AngII) infusion and the effect of treatment with the COX-2 inhibitor celecoxib was examined when initiated at different stages of the disease. Celecoxib treatment that was started 1 week after initiating AngII infusion reduced AAA incidence by 61% and significantly decreased AAA severity. Mice treated with celecoxib also showed significantly reduced aortic rupture and mortality. Treatment with celecoxib that was started at a late stage of AAA development also significantly reduced AAA incidence and severity. Celecoxib treatment significantly increased smooth muscle alpha-actin expression in the abdominal aorta and did not reduce expression of markers of macrophage-dependent inflammation. These findings indicate that COX-2 inhibitor treatment initiated after formation of AngII-induced AAAs effectively reduces progression of the disease in hyperlipidemic mice.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Sarbani
authors.initials: S
authors.lastname: Ghoshal
authors.forename: Charles D
authors.initials: CD
authors.lastname: Loftin
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D001019:Aortic Rupture / Q000209:etiology; D001057:Apolipoproteins E / Q000172:deficiency; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018450:Disease Progression; D006949:Hyperlipidemias / Q000150:complications*; D015994:Incidence; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2