Cyclooxygenase‐2 inhibition attenuates progression of abdominal aortic aneurysms in mice by regulating the smooth muscle cell phenotype

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. Human aneurysmal tissue is characterized by increased expression of cyclooxygenase‐2 (COX‐2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that inactivation of COX‐2 prior to disease initiation reduces AAA incidence. The objective of the current study was to determine the effectiveness of COX‐2 inhibition after initiation of the disease. Mice were treated with or without celecoxib after beginning AngII infusion, and AAA development was analyzed at different time‐points. The celecoxib treated mice had a significantly reduced incidence of AAAs and were protected from aortic rupture and death. The effectiveness of celecoxib was associated with significantly increased mRNA expression of markers of differentiated smooth muscle cell (SMC) phenotype including α‐actin, SM22α, desmin, myosin heavy chain 11 and smoothelin. Celecoxib treatment also decreased mRNA expression of a marker of dedifferentiated SMC (hyaluronic acid synthase 2). Similarly, in cultured aortic SMCs, celecoxib treatment increased expression of a marker of SMC differentiation. These findings suggest that COX‐2 inhibition attenuates progression of AAAs by maintaining a differentiated phenotype in abdominal aortic SMCs. Research support: NIH, HL083122