Effect of miR-369-5p on gene expression in endothelial cells and its possible relation to Sickle Cell Disease complications

Our recent studies demonstrate that circulating small Extracellular Vesicles (EVs) contribute to the abnormal endothelium in Sickle cell disease (SCD). EVs isolated from patients with SCD cause endothelial damage in vitro, in particular when patients experience complications, like Acute Chest Syndrome (ACS). By sequencing the miRNA contents of EVs isolated from patients with SCD, we identified a microRNA (miR-369-5p) that is highly specific to patients with a history of ACS and increases dramatically during an episode of ACS. Treatment of cells with miR-369-5p disrupts intact monolayers of human microvascular endothelial cells in a similar manner to the effect caused by EVs isolated from patients experiencing ACS. We hypothesized that miR-369-5p at least partially contributes to the impact of SCD-derived EVs on endothelium. In the current study, we performed RNA-seq after transfecting endothelial cells with miRNA-369-5p or negative control miRNA to identify pathways that are regulated by miR-369-5p and to understand their impact within the endothelium.