Reduced serum protease activity in Complex Regional Pain Syndrome: The impact of angiotensin-converting enzyme and carboxypeptidases.

Complex Regional Pain Syndrome (CRPS) occurs in about 2% of patients after fracture of the limbs. In an earlier clinical study with 102 probands we have shown that the serum protease network in CRPS might be less effective. Based on these results we hypothesized that angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) activity contribute to the differences of labeled bradykinin (DBK) degradation by patients' sera. Details of the enzymatic processes remained however unclear. The contributions of ACE and CPN in the serum degradation of DBK were studied using specific inhibitors. CPN1-ELISA was performed in serum. It was confirmed that the majority of DBK was degraded by ACE and CPN. The data delivered proof that the ACE serum activity was lowered in CRPS. High-resolution mass spectrometry was additionally used for protein expression analysis of sera of above study cohort (CRPS vs. healthy probands). According to principal component analysis of these data, significant differences between CRPS and control samples only occurred in sera of females younger than 46 years. In these CRPS patients, a number of defence / immunity-related proteins and members of the renin-angiotensin system (RAS) protein network were regulated. The impact of CPN in CRPS pathophysiology is subject to further investigation. The data support the hypothesis that both the RAS and the innate immune system might be affected in CRPS. A database of regulated serum proteins was established for future research.

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Declaration of Competing Interest The authors declare no conflict of interest.