Elevated plasma levels of matrix metalloproteinase-9 in patients with abdominal aortic aneurysms: A circulating marker of degenerative aneurysm disease

PURPOSE: Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdo minal aortic aneurysms (AAAs), where it plays a pivotal role in connective tissue destruction, Elevated plasma concentrations of MMP-9 (MMP-9(PL)) als o have been reported in patients with AAAs, but it is unclear if this can d istinguish patients with AAAs from those with atherosclerotic occlusive dis ease (AOD), The purpose of this study was to further define the utility of elevated MMP-9(PL) levels in the diagnosis and evaluation of AAAs, and to e xamine if changes in MMP-9(PL) can be used as a functional biomarker of deg enerative aneurysm disease, MATERIALS AND METHODS: Peripheral venous blood was obtained from 25 patient s with AAAs, 15 patients with AOD, and five normal control subjects, MMP-9( PL) levels were determined by an enzyme-linked immunosorbent assay, In four patients undergoing open AAA repair, MMP-9(PL) levels were directly compar ed with the amount of MMP-9 produced in aortic tissue, Six additional patie nts undergoing operative AAA repair were followed for 3-10 months to determ ine how treatment affected elevated MMP-9(PL) concentrations. RESULTS: Mean (+/-SE) MMP-9(PL) was 36.1 +/- 7.7 ng/mL in normal control su bjects, 54.7 +/- 10.5 ng/mL in patients with AOD, and 99.4 +/- 17.4 ng/mL i n patients with AAAs (P <.05 versus normal control subjects and patients wi th AOD), Elevated MMP-9(PL) levels (> 87.8 ng/mL) were found in 12 of 25 (4 8%) patients with AAA but in only one of 15 (7%) patients with AOD (P < .05 ), MMP-9(PL) levels did not correlate significantly with either age, gender , or aneurysm diameter, although there was a trend toward the highest value s in male patients with large AAAs. Production of MMP-9 in aneurysm tissues paralleled MMP-9(PL) levels, and elevated MMP-9(PL) levels decreased by 92 .7% +/- 3.2% after surgical AAA repair, CONCLUSIONS: Elevated MMP-9(PL) levels were observed in approximately one h alf of patients with AAAs and less than 10% of those with AOD (positive pre dictive value of 92.3%), but normal MMP-9(PL) levels had limited utility in excluding the presence of an aortic aneurysm (negative predictive value, 5 2%). MMP-9(PL) levels in patients with AAAs appeared to directly reflect th e amount of MMP-9 produced within aneurysm tissue, and MMP-9(PL) levels dec reased substantially after aneurysm repair. Measures of circulating MMP-9 m ay provide a biologically relevant marker of connective tissue metabolism i n patients with AAAs.