Abstract 17039: Aptamer-based Proteomic Profiling Reveals Novel Candidate Biomarkers of Myocardial Injury
Background: Emerging proteomic technologies are beginning to permit the systematic characterization of human plasma samples. DNA-aptamer based technologies may address limitations of existing proteomic techniques, including low sample throughput and limited dynamic range. Here we tested whether aptamer proteomics could identify novel early markers of myocardial injury.
Methods: We applied a single-stranded DNA aptamer-based technique that measures >1100 proteins to samples from individuals undergoing a planned myocardial infarction (PMI; alcohol septal ablation for hypertrophic cardiomyopathy). Serial blood samples were obtained before, at 10 and 60 minutes after PMI. Patients undergoing elective diagnostic coronary angiography served as negative controls. To further assess the generalizability of our PMI findings, we profiled samples from spontaneous MI (SMI) patients.
Results: There were 217 proteins that changed in the peripheral blood post ablation in a PMI derivation cohort (n=15; P < 5.70E-5, one-way ANOVA repeated measures). Seventy-nine of these proteins were validated in an independent PMI cohort (n=15; P < 2.30E-4, one-way ANOVA repeated measures); > 85% were directionally consistent and reached nominal significance in the validation cohort. Many protein changes detected are novel in the context of myocardial injury, including Dickkopf related protein 4, a WNT pathway inhibitor (peak increase 124%, P = 1.29E-15) and cripto, a growth factor important in cardiac development (peak increase 64%, P = 1.74E-4). Among the 40 proteins that were increased 1 hour after PMI, 23 were elevated in SMI (n=46; P < 0.05).
Conclusions: Aptamer-based proteomic scans detected new candidate biomarkers of myocardial injury, including many low abundance proteins. These findings motivate additional studies in larger, heterogeneous patient cohorts with spontaneous coronary syndromes.
Author Disclosures: D. Ngo: None. S. Sinha: None. D. Shen: None. M.J. Keyes: None. X. Shi: None. J.F. O’ Sullivan: None. L. Farrell: None. M.A. Fifer: None. M.S. Sabatine: None. R.E. Gerszten: None.
- © 2016 by American Heart Association, Inc.