Pro-Inflammatory Derangement of the Immuno-Interactome in Heart Failure

Figures

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  Figure 1. Distribution of immune cells in healthy controls patients with history of heart failure (HF). Heart disease was further categorized based on left ventricular ejection fraction levels into preserve ejection fraction (pEF) or reduced ejection fraction (rEF). (A, C) Figure shows distribution of immune cell types on t-SNE density map. Area with higher number of cells are reflected as dense clouds of yellow colors. For normalization, 100k cells were randomly sample from each category (HC n=18, CHF n=32, HFpEF n=14, HFrEF n=14) for visualization. (B, D) Expression of markers were overplayed on t-SNE map to show the phenotype of immune cells. (A, B) Shows the results from Panel 1 antibody staining while (C, D) shows results from Panel 2 antibody staining.

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  Figure 2. (A–E) Frequency of modulated Immune cell subset in Heart Failure (HF n=32) patients compared to Healthy Controls (HC, n=18). Frequency of significantly altered cell subsets in heart failure (HF) cases when compared to healthy control (HC) were shown as box and whisker plots. Phenotypes of the immune cell subsets that are significantly altered in Heart Failure cases are shown as heatmap. Median intensity was scaled normalized for heatmap visualization. Heatmap shows phenotypes of nodes found significantly altered from Panel 1 CyTOF analysis (F) and Panel 2 CyTOF analysis (G).

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  Figure 3. Co-regulatory network of immune subsets in heart failure (HF) disease shows highly modular structure compared to healthy controls (HC). Network analysis shows increased intracellular interaction of B and NK cells in the HF immunome network (A) compared to HC immune cell network (B). Network of nodes (cellular subsets) were created and plotted as force directed layout. The color of the nodes indicates the cellular phenotypes. The edges (line connecting the two nodes) represent the connection between the nodes. The colors of the edges indicate the correlation direction: red = positive, green = negative. Absolute correlation cutoff of 0.6 or greater were used to established edge between two nodes.

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  Figure 4. Immune cells modulated in Heart Failure cases categorized on the basis of left ventricular ejection fraction. (A) Frequency of significantly modulated Immune cell subset in patients with Heart Failure with preserved ejection fraction [HFpEF(n=14)] compared to Heart Failure patients with reduced ejection fraction [HFrEF(n=14)]. Frequency of significantly altered cell subsets is shown as box and whisker plots. (B) Phenotypes of the significantly altered immune subsets is shown as heatmap. Normalize median intensity of each marker used to plot heatmap.