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

Figures

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  Fig. 1. Experimental design. Created with BioRender.com

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  Fig. 2. Identification of 5 proteins as reflective indicators of cardiac physiology responses to myocardial infarction (MI). A Cardiac physiology of cohort 1 measured by echocardiography; values are average ± SEM. B Correlation heatmap of the top 5 protein candidates (ApoA1, haptoglobin, IgA, IL-17E, and TIMP-1) with the 6 cardiac physiology parameters (end systolic and diastolic dimensions and volumes, infarct wall thickness, and ejection fraction). C A representative correlation: ApoA1 negatively correlated with infarct wall thickness

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  Fig. 3. ApoA1, IL-17E, IgA, and TIMP1 increased after myocardial infarction (MI). A ApoA1 increased over the course of MI. ApoA1 increased from D0 to MI D3 in the retrospective plasma analysis (left). ApoA1 further increased from MI D3 to D7 in the prospective plasma analysis (right). B IgA, IL-17E, and TIMP-1 followed the same pattern as apoA1. The table summarizes protein expression in the plasma for both cohort 1 (D0 vs. D3) and cohort 2 (D3 vs. D7). Values are average ± SEM

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  Fig. 4. Validation in perspective cohort 2 for the 4 proteins, all of which mirrored cardiac physiology by regression analysis. A Cardiac physiology of cohort 2 measured by echocardiography. Values are average ± SEM. B Correlation heatmap of the top 4 plasma protein candidates (ApoA1, IgA, IL-17E, and TIMP-1) with the 6 cardiac physiology parameters (end systolic and diastolic dimensions and volumes, infarct wall thickness, and ejection fraction), as well as infarct size evaluated at necropsy. These 4 proteins offered extended predictability and mirrored cardiac physiology at MI D7. C A representative correlation: ApoA1 positively correlated with end systolic volume

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  Fig. 5. Haptoglobin increased early from D0 to MI D3 and decreased later from D3 to D7. A Haptoglobin expression peaked at MI D3. Haptoglobin increased from D0 to MI D3 in the retrospective plasma analysis (left). Haptoglobin decreased from MI D3 to D7 in the prospective plasma analysis (right). B Correlation heatmap of D7 plasma haptoglobin expression with D3 plasma expression and the D7 cardiac physiology variables

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  Fig. 6. Human glycoproteomic analysis showed that ApoA1, IL-17E, TIMP-1, and haptoglobin all signaled primarily through cytokine-cytokine receptor signaling after MI. A Protein–protein interactions among each identified plasma marker and the 999 other glycoproteins measured in the array showed enrichment of FOXM1 (ApoA1), STAT1 (IL-17E), STAT3 (haptoglobin), and USF2 (TIMP-1) transcription factors. B Cytokine-cytokine receptor signaling was the most enriched pathway as shown in the bubble chart

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  Fig. 7. We identified four plasma proteins — ApoA1, IgA, IL-17E, and TIMP-1 — involved in MI wound repair that mirror current and predict the future continuation of adverse cardiac remodeling. Created with BioRender.com