SIZE MATTERS - THE RELATIONSHIP BETWEEN MMP-9 EXPRESSION AND AORTIC DIAMETER

Background Despite a wealth of data detailing increased metalloprotein ase (MMP)-9 expression and activity in abdominal aortic aneurysms (AAA s), no studies examine the relationship between aortic size and MMP-9 expression. Because elastolysis occurs early in AAA formation, we hypo thesized that MMP-9 expression would vary with aortic diameter. The pu rpose of this study was to measure MMP-9 mRNA levels in AAAs of variou s diameters and define the relationship between AAA size and MMP-9 exp ression. Methods and Results MMP-9 mRNA levels were measured by compet itive polymerase chain reaction (PCR) using gene-specific external sta ndards with cDNA from AAAs (n = 19) and normal aortas (n = 4). Levels were normalized to GAPDH mRNA, determined separately via competitive P CR, to control for efficiency of reverse transcription. AAA size was m easured on CT scans obtained within 6 weeks of surgery. MMP-9/ GAPDH m RNA transcript levels in AAAs were expressed as mean +/- SEM and analy zed by ANOVA with a Tukey adjustment. There was a fourfold elevation i n MMP-9/GAPDH mRNA transcript levels in 5.0- to 6.9-cm AAAs (98.06 +/- 15.19) compared with small (3.0- to 4.9-cm) AAAs (20.87 +/- 5.15, P < .03), large (>7-cm) AAAs (27.16 +/- 14.56, P < .01), or normal aortas (3.57 +/- 1.13, P < .003). The results did not change when they were normalized to patient height, nor were there significant differences i n risk factors, age, or sex in each AAA group. Conclusions MMP-9 mRNA expression is significantly higher in moderate-diameter (5- to 6.9-cm) AAAs than either small (<4.0-cm) or large (>7.0-cm) AAAs. Increased M MP-9 expression may account for the propensity of AAAs >5 cm to contin ue to expand, in contrast to smaller aneurysms. Lower levels in AAAs > 7 cm suggest that increases in other enzymes or in diameter-dependent mechanical stress on the aortic wall are responsible for their charact eristic rapid expansion and high rupture rates.