MF-tricyclic inhibits growth of experimental abdominal aortic aneurysms.
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.
Keeling
W Brent
WB
University of South Florida Division of Vascular and Endovascular Surgery, Tampa, Florida 33606, USA.
Hackmann
Amy E
AE
Colter
Mary E
ME
Stone
Patrick A
PA
Johnson
Brad L
BL
Back
Martin R
MR
Bandyk
Dennis F
DF
Shames
Murray L
ML
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004549:Elastin / Q000032:analysis; D005663:Furans / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D052246:Cyclooxygenase 2 Inhibitors; D005663:Furans; C102563:3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone; D004549:Elastin; D020780:Matrix Metalloproteinase 9