Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms.
OBJECTIVE
The maintenance of an arterial elastin's integrity is essential in the prevention of abdominal aortic aneurysm (AAA) development. So far, the effect of intraluminal thrombus (ILT) thickness on the elastolytic activity within the AAA wall has not been studied. In the present study the hypothesis that thin thrombus is associated with enhanced proteolytic activity within human AAA wall was investigated.


METHODS
The specimens for analysis, from both thin (< or = 10 mm) thrombus-covered and thick (> or = 25 mm) thrombus-covered wall, had been taken from 40 patients undergoing elective repair of AAA. We evaluated neutrophil elastase activity with the enzymatic assay. Concentrations of active matrix metalloproteinase-9 (MMP-9), total matrix metalloproteinase-8 (MMP-8), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were measured by ELISA. Biochemical parameters were compared with the Wilcoxon signed-rank test.


RESULTS
Statistical analysis showed that the activity of elastase (P<0.0001) as well as concentrations of active MMP-9 (P=0.001), total MMP-8 (P<0.0001) and active MMP-9/total TIMP-1 ratio (P=0.002) were significantly higher in the thin thrombus-covered wall. Furthermore the TIMP-1 was found to have a lower concentration in the thin thrombus-covered in comparison with the thick thrombus-covered wall (P=0.003). There was a significant positive correlation between measurements in AAA wall sites with thin and thick thrombus for elastase, TIMP-1, MMP-9/TIMP-1 ratio, and a borderline correlation was observed for MMP-8. Active MMP-9 concentration did not correlate between sites.


CONCLUSIONS
The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.
Wiernicki
Ireneusz
I
Department of Vascular Surgery and Angiology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland. irekwie@wp.eu
Stachowska
Ewa
E
Safranow
Krzysztof
K
Cnotliwy
Miloslaw
M
Rybicka
Marta
M
Kaczmarczyk
Mariusz
M
Gutowski
Piotr
P
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000601:surgery; D001019:Aortic Rupture / Q000201:enzymology / Q000209:etiology; D001027:Aortography / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000032:analysis*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D011044:Poland; D011446:Prospective Studies; D013927:Thrombosis / Q000201:enzymology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
D019715:Tissue Inhibitor of Metalloproteinase-1; D019272:Leukocyte Elastase; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9