Characterization of differentially expressed plasma proteins in patients with acute myocardial infarction.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Novel biomarkers are needed to identify NSTEMI in AMI patients. The study objective was to use proteomics to identify novel plasma biomarkers for STEMI and NSTEMI patients. iTRAQ analysis was performed on pooled samples from 8 healthy controls and 12 STEMI and 12 NSTEMI patients. Bioinformatics analysis identified 95 differentially expressed proteins that were differentially expressed in the plasma of AMI patients and healthy controls; 28 of these proteins were found in STEMI/Con (22 upregulated and 6 downregulated), 48 in NSTEMI/Con (12 upregulated and 36 downregulated), and 44 in NSTEMI/STEMI (11 upregulated and 33 downregulated). Protein network analysis was then performed using STRING software. Functional analysis revealed that the identified plasma proteins were mainly involved with carbon metabolism, toll-like receptor signaling pathway, and hypertrophic cardiomyopathy. Nine of the proteins (SSA1, MDH1, FCN2, GPI, S100A8, LBP, vinculin, VDBP, and RBP4) that changed levels during AMI progression were further validated by ELISA. The constructed plasma proteome could reflect the AMI pathogenesis molecular mechanisms and provide a method for the early identification of NSTEMI in AMI patients. SIGNIFICANCE: The aim of this study was to use proteomics to identify novel predictive plasma biomarkers for patients with acute myocardial infarction (AMI), which would allow for either identification of individuals at risk of an infarction, and early identification of NSTEMI in patients with AMI. Using an approach that combined iTRAQ with LC-MS/MS, we found 95 proteins that showed significant differences in expression levels among the AMI patients and healthy controls. The proteins SSA1, MDH1, FCN2, GPI, S100A8, LBP, vinculin, VDBP, and RBP4 were found to play crucial roles in the pathogenesis of AMI. Using bioinformatics analysis, we found that dysregulation of carbon metabolism, toll-like receptor signaling pathway, and hypertrophic cardiomyopathy may be the major driving forces for cardiac damage during myocardial infarction. However, further investigations are needed to verify the mechanisms involved in the development of AMI especially NSTEMI. Taken together, our findings lay the foundation for understanding the molecular mechanisms underlying the pathogenic processes of AMI, and suggest potential applications for specific biomarkers in early diagnosis and determination of prognosis.