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Cathepsins and the activation of MMPs in abdominal aortic aneurysms (AAAs) wall

Objectives: Cathepsins are potent cysteine proteases that can degrade elastin in the aortic wall. They can activate other proteases such as MMPs contributing to aneurysm formation and expansion. The aim of this study was to determine the protein expression and activity of cathepsins and their inhibitors in AAA and aortic occlusive disease (AOD). We also examined their relationship with matrix metalloproteinase-9 activity.
Methods: Aortic wall was obtained from patients with AAA (n= 82), and AOD (n=13). The protein expression and activity of cathepsins B, H, K, L and S, and cystatins A, B, and C were measured by ELISA and specific fluorogenic substrates. MMP-9 activity was measured by bioimmunoassay.
Results: AAA wall had lower cystatin C levels (p = 0.03) and higher levels of cathepsin H protein (p = 0.007) compared with AOD. The activity of cathepsins B, H, L, and S was significantly greater in AAA than AOD. In AAA wall, MMP9 activity was positively correlated with cathepsin L activity (Pearson r=0.42, P <0.0001) and negatively correlated with cystatin C levels (Pearson r= - 0.75, P <0.0001).
Conclusions: There is evidence of an imbalance between the activity of cysteine proteases and cystatin C in the aneurysmal wall. There is also evidence of a relationship between both cystatin C and cathepsin L and activation of a major matrix-remodelling enzyme, MMP9.