The Transcriptional Profile of Iron Deficiency in Patients with Heart Failure: Heme-Sparing and Reduced Immune Processes

Figures

• 

  Figure 1. Volcano plot showing differentially expressed genes between patients with and without iron deficiency. Each dot represents one of the 17 900 genes quantified in the whole blood microarray in 881 patients. On the x‐axis, the log2‐fold change in gene expression is depicted (positive log2‐fold change is higher biomarker expression in patients with iron deficiency; negative log2‐fold change is lower biomarker expression in patients with iron deficiency), while the y‐axis shows the magnitude of the biomarker expression difference as –log10 of the p‐value. Green dots indicate biomarkers that are not significantly different, orange dots represent biomarkers that are significantly different with a log2‐fold change between −0.4 and 0.4, purple dots represent biomarkers that are significantly different and have a log2‐fold change of ≥0.4 or ≤−0.4. Significance was tested using a logistic multivariable model adjusted for multiple testing based on the Benjamini–Hochberg method.

• 

  Figure 2. Significantly up‐ or downregulated gene expression networks in patients with iron deficiency as compared to no iron deficiency.

• 

  Figure 3. Gene set enrichment analyses for heme and iron–sulfur associated pathways. Barcode plot, each vertical line depicts a single gene, with the red lines representing genes of the heme pathway (153 genes) and the blue lines representing genes of the iron–sulfur cluster pathway (24 genes). In case a gene is located to the left (blue area) it is downregulated while it is upregulated when it appears on the rights (red area). It can be observed that blue genes (iron–sulfur cluster related) are downregulated and thus cluster mainly to the left, while the opposite is true for the red genes (heme related), which cluster to the right.

• 

  Figure 4. Gene expression in human cardiomyocytes of upregulated genes in whole blood. Gene expression levels relative to control conditions (ctrl) for iron‐deficient cardiomyocytes (iron deficient) after 4 days of exposure to deferoxamine and iron supplemented cardiomyocytes (transferrin treated) who were first subjected to 4 days of deferoxamine and subsequently treated with transferrin bound iron for 3 days. Biological replicates were 14 ctrl, 12 iron deficient and 8 transferrin treated, 2 technical replicates were performed. *p < 0.05, statistical test is the one‐way ANOVA with a post hoc Tukey's honestly significant difference test. CISD2, CDGSH iron–sulfur domain 2; CLIC2, chloride intracellular channel protein 2; CLIC4, chloride intracellular channel protein 4; CTNNAL1, alpha‐catulin; SIAH2, E3 ubiquitin‐protein ligase siah2; SLC22A4, solute carrier family 22; TMOD1, tropomodulin 1.