Cathepsin enzymes and cystatin C : Do they play a role in positive arterial remodeling?

We have read the impressive article recently published by Aoki et al1 evaluating the cathepsin enzyme system in cerebral aneurysm formation. By using quantitative RT-PCR and im munohistochemistry, the authors have demonstrated increased expression of cathepsin B, cathepsin K, and cathepsin S in arterial wall of the cerebral aneurysms, whereas the expres sion of cystatin C was found to be decreased. These findings suggest an imbalance between cysteine cathepsins and their inhibitor. This imbalance may cause the excessive breakdown of extracellular matrix in the arterial wall resulting in pro gressing arterial aneurysm formation. This conclusion was supported by the experimental use of the cathepsin inhibitor NC-2300.