Tanscriptional profile of primary endothelial cells (HUVEC) in ADA2 depleted setting and effect of Dipyridamole (DPM) treatment. Tanscriptional profile of primary endothelial cells (HUVEC) in ADA2 depleted setting and effect of Dipyridamole (DPM) treatment

Adenosine deaminase 2 deficiency (DADA2) is an inherited disorder which can cause vasculitis of medium-sized blood vessels. The disease is caused by mutations in the CECR1 gene, which encodes a key metabolic enzyme in the purine pathway. It is not clear how DADA2 leads to vasculitis, and there are currently limited treatment options. We, therefore, as a first step aimed to study the altered gene expression profile of primary endothelial cells in ADA2 depleted setting and then assessed the effect of Dipyridamole (DPM), a pharmacological inhibitor of ENT- transporters, on the differentially expressed genes. The whole genome transcriptome analysis revealed a robust induction of an IFNβ-stimulated gene signature in unstimulated siADA2-treated cells. Differentially expressed transcripts in this dataset included genes encoding pro-inflammatory cytokines, chemokines, and innate immune response proteins. Pre-treatment with dipyridamole (DPM), reduced expression of the IFNβ-driven gene signature upon depletion of ADA2. Overall design: Two experiments were performed. In the first experiment 2 conditions in triplicates were considered: 1. HUVEC transfected with non-targeting si RNA referred to as siControl 2. HUVECs transfected with siRNA targeing ADA2 molecule referred to as siADA2. In the second experiment 3 conditions in triplicates were considered: 1. HUVEC transfected with non-targeting si RNA referred to as control 2. HUVECs transfected with siRNA targeing ADA2 molecule referred to as CECR1 3. HUVECs transfected with siRNA targeing ADA2 molecule and pre-treated with Dipyridamole (DPM) refrered as CECR1_DPM