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 IFNß-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 IFNß-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