MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms

• Published in: The Journal of surgical research 2007-08, Vol.141 (2), p.192-195
• Main Authors: Keeling, W. Brent, M.D, Hackmann, Amy E., M.D, Colter, Mary E., Ph.D, Stone, Patrick A., M.D, Johnson, Brad L., M.D, Back, Martin R., M.D, Bandyk, Dennis F., M.D, Shames, Murray L., M.D
• Format: Article
• Language: English
• Subjects: Animals; Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - pathology; Biological and medical sciences; CaM; CV159; Cyclooxygenase 2 Inhibitors - therapeutic use; Elastin - analysis; ex vivo EPR; Furans - therapeutic use; General aspects; hepatic IR injury; in vivo EPR; Male; Matrix Metalloproteinase 9 - genetics; Medical sciences; Rats; Rats, Sprague-Dawley; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2006.12.544

Background Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (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 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 postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. Results Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 ± 0.1 mm versus 2.4 ± 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 ± 8.5% versus 132.3 ± 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) ( P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. Conclusions COX-2 inhibition helps to retard the growth of experimental AAAs 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. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.