Quantitative Proteomics for Cardiac Biomarker Discovery Using Isoproterenol-Treated Nonhuman Primates

To identify
new cardiac biomarkers, a quantitative proteomic analysis has been
performed on serum and heart tissue proteins from three species of
nonhuman primates following isoproterenol (ISO) treatment. Three serum
proteinsserum amyloid A (SAA), α-1-acid glycoprotein
(A1AG), and apolipoprotein A-1 (Apo A1)were consistently identified
as changed and remained altered 72 h post dose in all three species
post ISO treatment, indicating the potential of including these proteins
in preclinical or clinical evaluation of drug-induced cardiac injury.
Furthermore, proteomic analysis of heart tissue proteins following
ISO treatment demonstrated detrimental effects on calcium signaling
and energy generation in cardiac myocytes. It is worth noting that
cardiac troponins were not identified in serum but were identified
as altered in heart tissue lysate along with other cardiac-specific
proteins. This strategy for cardiac biomarker discovery by proteomic
screening of heart tissue proteins, followed by verification in serum
samples using immunoassays or targeted mass spectrometry, could be
applied in future biomarker studies.