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Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms

      Abstract

      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 (≤10 mm) thrombus-covered and thick (≥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.

      Conclusion

      The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.

      Keywords

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