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

William D. McMillan, Natalia A. Tamarina, Maria Cipollone, David A. Johnson, Michele A. Parker, William H. Pearce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

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 AAA (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) AAA (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.

Original languageEnglish (US)
Pages (from-to)2228-2232
Number of pages5
JournalCirculation
Volume96
Issue number7
DOIs
StatePublished - Oct 7 1997

Keywords

  • Aneurysm
  • Aorta
  • Metalloproteinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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