Improvements in long-term
cancer survival rates have resulted in an increase in the prevalence of
chemotherapy-linked
cardiac failure, but treatment-induced cardiac
injuries may not be detected until long after
therapy. Monitoring cardiac function is recommended; however, cardiovascular injury in
cancer patients differs from those with primary cardiac dysfunction, which limits the utility of traditional cardiac
biomarkers. Here we examined plasma levels of
peptides produced by
cathepsin B, which is released during
chemotherapy-induced cardiac injury. We applied nanotrap fractionation to enrich plasma
peptides from
cancer patients treated with or without
chemotherapy.
Peptides associated with
chemotherapy-induced
cardiotoxicity, but not other cardiac injury, were identified by mass spectrometry, and their dependence on
cathepsin B activity was determined using
enzyme inhibition experiments. We found that a
peptide (SAA-1525) derived from serum
amyloid A1 was significantly increased in
cardiotoxicity patients, and its production was inhibited when plasma samples were pretreated with
cathepsin B specific inhibitors. Plasma SAA-1525 also correlated with other markers of cardiac injury. Analysis of plasma SAA-1525 levels may hold potential as a rapid and minimally invasive method to monitor subclinical injury, thereby allowing timely intervention to mitigate further cardiac damage and avoid more severe clinical presentation.