Size matters: the relationship between MMP-9 expression and aortic diameter.
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.


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.
McMillan
W D
WD
Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Ill, USA.
Tamarina
N A
NA
Cipollone
M
M
Johnson
D A
DA
Parker
M A
MA
Pearce
W H
WH
D000368:Aged; D001012:Aorta, Abdominal / Q000033:anatomy & histology* / Q000201:enzymology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D017364:Collagenases / Q000096:biosynthesis*; D018076:DNA, Complementary; D003925:Diabetic Angiopathies; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D012907:Smoking; D014158:Transcription, Genetic
D018076:DNA, Complementary; D012333:RNA, Messenger; D017364:Collagenases; D020780:Matrix Metalloproteinase 9