EXPRESSION OF MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN ANEURYSMS AND NORMAL AORTA

Background. Abdominal aortic aneurysms (AAAs) are characterized by deg radation of collagen and elastin resulting from increases in matrix me talloproteinase (MMP) activity. Previous authors have identified isola ted increases in expression of specific MMPs in AAAs, but none have co mpared relative levels of expression of particular MMPs to one another or to those of their inhibitors, the tissue inhibitors of metalloprot einases (TIMPs). This study proposes to quantify relative mRNA levels for interstitial collagenase (MMP-1), 72 kd type IV collagenase (MMP-2 ), 92 kd type IV collagenase (MMP-9), TIMP-1, and TIMP-2 in normal aor ta (NA) and AAA to provide insight as to the relative importance of ea ch in aneurysm formation. Methods. Competitive polymerase chain reacti ons (PCRs) with gene-specific external standards and cDNA derived from AAAs (n = 8; mean age, 67.4 years) and NA (n = 5; mean age, 40.6 year s) were used to quantify mRNA levels. Results were normalized to glyce raldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels, determined by means of competitive PCR, and compared by means of Mann-Whitney stati stics. Results. Significant increases in MMP mRNA expression in AAA ov er NA were observed for MMP-1 (3.64 versus 0.43, p = 0.007), MMP-9 (78 .03 versus 3.35, P = 0.003), TIMP-1 (835.32 versus 477.2, p = 0.027), and TIMP-2 (18.09 versus 4.14, p = 0.003). The ratio of MMP to TIMP mR NA levels was higher in AAA than NA (0.135 versus 0.045, p = 0.018). C onclusions. Increases in expression of MMP-1, MMP-9, and MMP/TIMP rati os may result in increased proteolysis and matrix degradation, which c haracterize AAAs. MMP-9 appears to be the predominant metalloproteinas e expressed in AAA, because its mRNA levels were more than 20 times an d 2 times higher than those of MMP-1 and MMP-2, respectively. TIMP-1 m RNA levels were in molar excess to those of any of the metalloproteina ses studied.