Harnessing the Plasma Proteome to Mirror Current and Predict Future Cardiac Remodeling After Myocardial Infarction

Abstract

To identify plasma proteins that mirror current and predict future remodeling after myocardial infarction (MI), we retrospectively interrogated plasma proteomes of day (D)0 control (n = 16) and D3 MI (n = 15) from C57BL/6 J mice (20 ± 1 months). A total of 165 unique proteins were correlated with cardiac physiology variables. We prospectively tested the hypothesis that candidates identified retrospectively would predict cardiac physiology at an extended timepoint (D7 MI) in a second cohort of mice (n = 4 ± 1 months). We also examined human plasma from healthy controls (n = 18) and patients 48 h after presentation for MI (n = 41). Retrospectively, we identified 5 strong reflectors of remodeling (all r ≥ 0.60 and p < 0.05). Prospectively, ApoA1, IgA, IL-17E, and TIMP-1 mirrored current and predicted future remodeling. In humans, cytokine-cytokine receptor signaling was the top enriched KEGG pathway for all candidates. In summary, we identified plasma proteins that serve as useful prognostic indicators of adverse remodeling and progression to heart failure. Graphical Abstract

From multi-omics approaches to personalized medicine in myocardial infarction

“…LVR is a prevalent complication following MI, and researchers have identified several potential protein biomarkers associated with this condition. These biomarkers include apolipoprotein A1, immunoglobulin A, interleukin-17E, tissue inhibitor of metalloproteinases-1, urokinase-type plasminogen activator, midkine, proprotein convertase subtilisin/kexin type 6, among others ( 170 , 173 , 174 ). Furthermore, proteomic studies can provide useful information in assessing left ventricular ejection fraction (LVEF) and infarct size after MI ( 175 ).…”