Project description:Inflammatory activation of endothelial cells is considered to be the first step in the development of atherosclerosis. Here, we determined changes of aortic gene expression after chronic inflammatory activation of arterial endothelial cells in genetically modified mice.
Project description:Vascular endothelial cells (ECs) form a dynamic interface between blood and tissue and play a crucial role in the progression of vascular inflammation. Here, we explored the underlying molecular mechanisms of endothelial-cytokine responses which govern inflammation. Applying an unbiased cytokine library, we determined TNFα and IFNγ induced the largest EC response and had distinct proteomic inflammatory signatures. Moreover, combined TNFα + IFNγ stimulation induced a third synergetic inflammatory state. We employed a multi-omics approach combining (phospho-) proteome, transcriptome and secretome to delineate these inflammatory states and found that endothelial cells contain a wide-array of immune-modulating capacities such as complement proteins, MHCI and MHCII complexes and distinct secretory cytokine production per stimulus. Synergy was regulated through cooperative interplay of transcript induction. This extensive resource describes the intricate molecular mechanisms that are at the basis of endothelial inflammation and supports the adaptive immunomodulatory role of the endothelium in host defense and vascular inflammation.
Project description: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.
Project description: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.
Project description:Vascular endothelial cells (ECs) form a dynamic interface between blood and tissue and play a crucial role in the progression of vascular inflammation. Here, we explored the underlying molecular mechanisms of endothelial-cytokine responses which govern inflammation. Applying an unbiased cytokine library, we determined TNFα and IFNγ induced the largest EC response and had distinct proteomic inflammatory signatures. Moreover, combined TNFα + IFNγ stimulation induced a third synergetic inflammatory state. We employed a multi-omics approach combining (phospho-) proteome, transcriptome and secretome to delineate these inflammatory states and found that endothelial cells contain a wide-array of immune-modulating capacities such as complement proteins, MHCI and MHCII complexes and distinct secretory cytokine production per stimulus. Synergy was regulated through cooperative interplay of transcript induction. This extensive resource describes the intricate molecular mechanisms that are at the basis of endothelial inflammation and supports the adaptive immunomodulatory role of the endothelium in host defense and vascular inflammation.
Project description:Inflammatory activation of endothelial cells is considered to be the first step in the development of atherosclerosis. Here, we determined the consequences of chronic endothelial NF-κB activation on the development and progression of atherosclerosis as well as plaque regression.