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Elevated Plasma Levels of Matrix Metalloproteinase-9 in Patients with Abdominal Aortic Aneurysms: A Circulating Marker of Degenerative Aneurysm Disease

2000; Elsevier BV; Volume: 11; Issue: 10 Linguagem: Inglês

10.1016/s1051-0443(07)61315-3

1535-7732

David M. Hovsepian, Scott J. Ziporin, Maromi K. Sakurai, Jason Lee, John A. Curci, Robert W. Thompson,

Aortic Disease and Treatment Approaches

PURPOSE Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), where it plays a pivotal role in connective tissue destruction. Elevated plasma concentrations of MMP-9 (MMP-9 PL ) also have been reported in patients with AAAs, but it is unclear if this can distinguish patients with AAAs from those with atherosclerotic occlusive disease (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 examine if changes in MMP-9 PL can be used as a functional biomarker of degenerative aneurysm disease. MATERIALS AND METHODS Peripheral venous blood was obtained from 25 patients 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 compared with the amount of MMP-9 produced in aortic tissue. Six additional patients undergoing operative AAA repair were followed for 3–10 months to determine how treatment affected elevated MMP-9 PL concentrations. RESULTS Mean (±SE) MMP-9 PL was 36.1 ± 7.7 ng/mL in normal control subjects, 54.7 ± 10.5 ng/mL in patients with AOD, and 99.4 ± 17.4 ng/mL in patients with AAAs ( P < .05 versus normal control subjects and patients with AOD). Elevated MMP-9 PL levels (> 87.8 ng/mL) were found in 12 of 25 (48%) 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 values 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 half of patients with AAAs and less than 10% of those with AOD (positive predictive value of 92.3%), but normal MMP-9 PL levels had limited utility in excluding the presence of an aortic aneurysm (negative predictive value, 52%). MMP-9 PL levels in patients with AAAs appeared to directly reflect the amount of MMP-9 produced within aneurysm tissue, and MMP-9 PL levels decreased substantially after aneurysm repair. Measures of circulating MMP-9 may provide a biologically relevant marker of connective tissue metabolism in patients with AAAs.