Elevated plasma levels of matrix metalloproteinase-9 in patients with abdominal aortic aneurysms: a circulating marker of degenerative aneurysm disease.
OBJECTIVE
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-9PL) 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-9PL levels in the diagnosis and evaluation of AAAs, and to examine if changes in MMP-9PL can be used as a functional biomarker of degenerative aneurysm disease.


METHODS
Peripheral venous blood was obtained from 25 patients with AAAs, 15 patients with AOD, and five normal control subjects. MMP-9PL levels were determined by an enzyme-linked immunosorbent assay. In four patients undergoing open AAA repair, MMP-9PL 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-9PL concentrations.


RESULTS
Mean (+/- SE) MMP-9PL 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-9PL 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-9PL 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-9PL levels, and elevated MMP-9PL levels decreased by 92.7% +/- 3.2% after surgical AAA repair.


CONCLUSIONS
Elevated MMP-9PL 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-9PL levels had limited utility in excluding the presence of an aortic aneurysm (negative predictive value, 52%). MMP-9PL levels in patients with AAAs appeared to directly reflect the amount of MMP-9 produced within aneurysm tissue, and MMP-9PL 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.
Hovsepian
D M
DM
Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA. havsepiand@mir.wustl.edu
Ziporin
S J
SJ
Sakurai
M K
MK
Lee
J K
JK
Curci
J A
JA
Thompson
R W
RW
D000328:Adult; D000704:Analysis of Variance; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9