Purpose: Previous investigators have identified disease-specific elevations of metalloelastase-9 (MMP-9) in aneurysm tissue biopsies. We hypothesized that circulating MMP-9 might also be elevated in patients with aneurysms. The purpose of this study was to compare plasma and aortic tissue MMP-9 levels in patients with infrarenal aneurysms (AAAs), patients with symptomatic aortoiliac occlusive disease (AOD), and healthy patients. Methods: A sandwich enzyme-linked immunosorbent assay was used to measure plasma MMP-9 in patients with AAA (n = 22; mean age, 72.7 years), with AOD (n = 9; mean age, 60.5 years), and without disease (n = 8; mean age, 35.3 years). The MMP-9 levels also were measured in 48-hour supernatants of organ culture tissue explants from patients with AAA (n = 10; mean age, 66.2 years) and AOD (n = 5; mean age, 50.4 years) and organ donors (n = 7; mean age, 48.1 years). The results were reported as the mean ± the standard error of the mean and analyzed with analysis of variance with multivariate regression. Results: The plasma MMP-9 levels were significantly higher in the patients with AAA (85.66 ng/mL ± 11.64) than in the patients with AOD (25.75 ng/mL ± 4.159; P < .001) or the healthy patients (13.16 ng/mL ± 1.94; P < .001). No significant difference in plasma MMP-9 levels between patients with AOD and healthy patients was identified. The patients with multiple aneurysms had significantly higher levels of plasma MMP-9 than did the patients with an isolated AAA (134.68 ng/mL ± 17.5 vs 71.03 ng/mL ± 10.7; P < .04). In organ culture, AAA and AOD tissue explants produced significantly higher levels of MMP-9 (3218.5 ng/gm ± 1115.2 and 1283.1 ng/gm ± 310.6 aortic tissue) than did disease free explants (6.14 ng/gm ± 2.3 aortic tissue; P < .0001). No significant difference in MMP-9 production between AAA and AOD explants was identified. Conclusion: Plasma MMP-9 levels are significantly higher in patients with AAA than in patients with AOD or in healthy volunteers. The patients with multiple aneurysms have higher levels than those patients with an isolated AAA. Organ culture studies suggest that diseased aortic tissue is the source of MMP-9.
McMillan, W. D., Pearce, W. H., Thompson, R. W., Baxter, B. T., Hunter, G. C., Baker, W. H., … Zarins, C. K. (1999). Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms. Journal of Vascular Surgery, 29(1), 122–129. https://doi.org/10.1016/S0741-5214(99)70363-0