(Circulation. 1997;96:2228-2232.)
© 1997 American Heart Association, Inc.
Articles |
Size Matters
The Relationship Between MMP-9 Expression and Aortic Diameter
From the Feinberg Cardiovascular Research Institute (D.A.J., M.A.P.) and Division of Vascular Surgery, Department of Surgery (W.D.M., N.A.T., M.C., W.H.P.), Northwestern University Medical School, Chicago, Ill.
Correspondence to William H. Pearce, MD, 251 E Chicago Ave, No. 626, Chicago, IL 60611.
Background Despite a wealth of data detailing increased metalloproteinase (MMP)-9 expression and activity in abdominal aortic aneurysms (AAAs), no studies examine the relationship between aortic size and MMP-9 expression. Because elastolysis occurs early in AAA formation, we hypothesized that MMP-9 expression would vary with aortic diameter. The purpose of this study was to measure MMP-9 mRNA levels in AAAs of various diameters and define the relationship between AAA size and MMP-9 expression.
Methods and Results MMP-9 mRNA levels were measured by competitive polymerase chain reaction (PCR) using gene-specific external standards with cDNA from AAAs (n=19) and normal aortas (n=4). Levels were normalized to GAPDH mRNA, determined separately via competitive PCR, to control for efficiency of reverse transcription. AAA size was measured on CT scans obtained within 6 weeks of surgery. MMP-9/GAPDH mRNA transcript levels in AAAs were expressed as mean±SEM and analyzed by ANOVA with a Tukey adjustment. There was a fourfold elevation in 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 in 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 MMP-9 expression may account for the propensity of AAAs >5 cm to continue 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 characteristic rapid expansion and high rupture rates.
Key Words: aorta • aneurysm • metalloproteinases
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