Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells. [ATAC-Seq]

Inflammatory stresses underlie endothelial dysfunction and contribute to the development of chronic cardiovascular disorders such as atherosclerosis and vascular fibrosis. The initial transcriptional response of endothelial cells to pro-inflammatory cytokines such as TNF-alpha is well established. However, very few studies uncover the effects of inflammatory stresses on chromatin architecture. We used integrative analysis of ATAC-seq and RNA-seq data to investigate chromatin alterations in human endothelial cells in response to TNF-alpha and febrile-range heat stress exposure. Multi-omics data analysis suggests a correlation between the transcription of stress-related genes and endothelial dysfunction drivers with chromatin regions exhibiting differential accessibility. Overall design: To investigate genome-wide changes in chromatin accessibility, we performed ATAC-seq on EC cells, exposed to either 2hr of 39ºC febrile-like heat stress or 6hr of 10 ng/ml TNF-alpha.