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

Abstract

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.