Iron chelation shifts endothelial phenotypes

Iron deficiency is a highly prevalent nutrient deficiency and the most common cause of anemia. Although iron deficiency exacerbates cardiovascular disease, the direct impact of iron deficiency on the vasculature remains unstudied. Human lymphatic and arterial endothelial cells were treated with deferoxamine for 24 hours to assess the impact of iron deficiency on endothelial cell phenotypes. We found iron chelation upregulated the expression of arterial makers in both cell types. In lymphatic endothelial cells, iron chelation decreased the expression of lymphatic markers. These data suggest iron chelation shifts endothelial cells toward an arterial phenotype. Overall design: To deplete iron, human coronary artery ECs and human dermal lymphatic ECs were grown to confluence and treated with 100 mM deferoxamine (DFO; MedChemExpress) for 24 hours. RNA was isolated with Quick-RNA MiniPrep (Zymo Research). PE150 reads were generated with the Illumina NovoSeq platform. The paired-end reads were mapped to the hg38 reference genome using STAR (v2.7.9a). Gene counts were generated with featureCounts in the Subread package. For all datasets, DESeq2 (v1.34.0) was used to identify differentially expressed genes (DEGs) (Padj < 0.05). Ensemble IDs were converted to gene symbols using the org.Hs.eg.db package.