Murray L Shames
University of South Florida, Tampa, FL
Objective: Experimental Abdominal Aortic Aneurysm (AAA) development can be pharmacologically suppressed by inhibiting MMP-9. Cox-2 inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic a selective Cox-2 inhibitor incorporated into rodent chow would inhibit aneurysm development in a rat AAA model.
Methods: Twelve male Sprague-Dawley rats underwent induction of experimental abdominal aortic aneurysms (AAA) using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and post-infusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for matrix metalloproteinase-9 (MMP-9), by immunohistochemistry for Cox-2, and by VVG staining for elastin.
Results: Elastase infusion produced AAA in all rats. At 14 days MF-trycyclic treated rats had significantly reduced AAA development (1.88+/- .06 mm vs. 2.43+/- .04 mm, p=.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng/ml vs. 1.114 ng/ml). Elastin was preserved in the MF-tricyclic treated aortas
Conclusions: Cox-2 inhibition helps to retard the growth of experimental AAA’s possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Cox-2 inhibition may offer an additional method to pharmacologically inhibit AAA’s.