The biological variation of serum ACE and CPN/CPB2 activity in healthy individuals as measured by the degradation of the neuro-peptide bradykinin – A reference dataset

Bradykinin (BK) is an inflammatory mediator. Its degradation in biofluids reports on the activity of enzymes like angioten-sin-converting enzyme (ACE) and basic carboxypeptidases N and CBP2 for which the neuropeptide is a substrate. Clinical studies have shown significant changes in the serum activity of these enzymes in patients with inflammatory diseases. Here, we investigated the natural variation of the cleavage of dabsylated BK in serum and the formation of two of its major fragments in a large cohort of 340 healthy volunteers from the international human Personal Omics Profiling (hPOP) consor-tium based at Stanford University. A batch effect was noted among sampling sites. In individual sample sets, it could be shown that the serum measured protease activity was statistically significantly higher in males than in females. Moreover, outliers were detected, which indicated a correlation of the experimental values and untreated diabetes and extensive exer-cising. There was no significant correlation with age, ethnicity, body mass index or overnight fasting. The investigation pro-vides reference values from the healthy population for the neuropeptide reporter assay. Importantly, the experiments were sensitive to sample quality and collection procedures – the results reiterate the importance of a high level of standardisation in preanalytical sample collection and processing.