pt9b00035_si_003.xlsx (10.05 kB)
Cathepsin B Dependent Cleavage Product of Serum Amyloid A1 Identifies Patients with Chemotherapy-Related Cardiotoxicity
dataset
posted on 2019-09-03, 17:04 authored by Fangfang Zhang, Christopher J. Lyon, Robert J. Walls, Bo Ning, Jia Fan, Tony Y. HuImprovements
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.