Abstract 17440: A Novel Aptamer-based Proteomic Technology for Cardiac Biomarker Discovery
Background: Current proteomic technologies have been slow to identify and validate new cardiac biomarkers. Chemically modified DNA-aptamers can serve as highly multiplexed immuno-like assays that offer the advantage of high-throughput for biomarker discovery.
Methods: We applied a novel aptamer-based technique (SOMAscan™) that measures > 1100 proteins to samples from individuals undergoing a “planned” myocardial infarction (PMI: alcohol ablation for hypertrophic cardiomyopathy), in which each individual serves as their own control. Serial blood samples were obtained before, 10 and 60 minutes after PMI. Patients undergoing elective diagnostic coronary angiography served as negative controls. Coronary sinus (CS) blood samples were collected concurrent with peripheral samples to determine potential myocardial origin of protein changes.
Results: There were 301 proteins that significantly changed in the peripheral blood post ablation in a PMI derivation cohort (n=15; p < 5.71E-5 , one-way ANOVA repeated measures), excluding proteins identified in the negative controls. Forty-three of these proteins were subsequently validated in a smaller PMI cohort (n=6; p < 1.66E-4, one-way ANOVA repeated measures), including known cardiac markers of injury such as troponin I (p= 5.24E-13) and CK-MB (p= 1.39E-10). Many protein changes detected are novel in the context of myocardial injury, including decreases in GDF-11 (p= 6.28E-5), a secreted factor shown to reverse age-related cardiac hypertrophy in mice and increases in PPIB (p= 2.30E-7), a cyclosporine-binding protein. Additionally, CS blood analysis confirmed 25 proteins as significantly changed after PMI, including 20 of the validated peripheral blood proteins (n=6; p < 5.71E-5, one-way ANOVA repeated measures). Furthermore, CS vs. peripheral blood comparison revealed 12 of the 301 proteins as significantly different (n=6; p < 5.71E-5, two-way ANOVA repeated measures), seven of which were enriched in the CS suggesting possible myocardial origin.
Conclusions: In pilot studies, an aptamer-based proteomic scan detected new biomarkers of myocardial injury. These findings motivate additional clinical studies in large, heterogeneous patient cohorts with spontaneous coronary syndromes.
Author Disclosures: D. Ngo: None. M.J. Keyes: None. R.E. Gerszten: None.
- © 2014 by American Heart Association, Inc.