Ontology highlight
ABSTRACT:
PROVIDER: PRJNA925697 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional mechanisms that drive angiogenesis and organotypic endothelial specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors. Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent VE-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this transcription factor. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of ß-catenin-dependent genes such as TCF/LEF1 and ZIC3 transcription factors, transporters and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 transcriptional factor gradient and enables organotypic endothelial specialization of the vascular network.
2019-12-05 | GSE141440 | GEO
Project description:Hyperglycemia-mediated cardiac dysfunction is an acute initiator in the development of vascular complications, leading to cardiac fibrosis. To investigate the effects of hyperglycemia-mediated changes in cardiomyocytes, cells were cultured in-vitro under normoglycemic (5 mM or 25 mM D-glucose) and hyperglycemic (5 → 50 mM or 25 → 50 mM D-glucose) conditions, respectively. After 24-hours of hyperglycemic exposure, cells were collected for RNA-sequencing (RNA-seq) studies to further investigate the differentially expressed genes (DEG) related to inflammation and fibrosis in samples cultured under hyperglycemic-in comparison with normoglycemic-conditions. Western Blotting was done to evaluate the protein expression of YAP1/TAZ under hyperglycemia induced stress conditions, as it is known to be involved in fibrotic and vascular inflammatory-mediated conditions. RNA-seq revealed the DEG of multiple targets including matrix metalloproteinases and inflammatory mediators, whose expression was significantly altered in the 5 → 50 mM in comparison with the 25 → 50 mM condition. Western Blotting showed a significant upregulation of the protein expression of the YAP1/TAZ pathway under these conditions as well (5 → 50 mM). To further probe the relationship between the inflammatory extracellular-signal-regulated kinase (ERK 1/2) and its downstream effects on YAP1/TAZ expression we studied the effect of inhibition of the ERK 1/2 signaling cascade in the 5 → 50 mM condition. The application of an ERK 1/2 inhibitor inhibited the expression of the YAP1/TAZ protein in the 5 → 50 mM condition, and this strategy may be useful in preventing and improving hyperglycemia associated cardiovascular damage and inflammation.
2024-02-23 | GSE223586 | GEO
Project description:Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, endothelial dysfunction and vascular complications of diabetes. MicroRNAs (miRNAs) play a role in the development of endothelial dysfunction in diabetes, with potential application for the future therapy of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemic condition. This study aimed to identify the miRNA profile of human umbilical vein endothelial cells (HUVEC) exposed to hyperglycemic state using RNA sequencing analysis.
2023-07-06 | GSE229207 | GEO
Project description:The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine (SAH) hydrolase (SAHH). Increasing intracellular adenosine by genetic ADK knockdown or exogenous adenosine reduces activation of the transmethylation pathway and attenuates the endothelial inflammatory response. In addition, loss of endothelial ADK in mice leads to reduced atherosclerosis and affords protection against ischemia/reperfusion injury of the cerebral cortex. Taken together, these results demonstrate that intracellular adenosine, which is controlled by the key molecular regulator ADK, influences endothelial inflammation and vascular inflammatory diseases. We knocked down the adenosine kinase (ADK) in human primary endothelial cells to study the endothelial inflammatory responses to ADK inactivation under static conditions.
2017-07-12 | GSE101126 | GEO
Project description:Myeloperoxidase (MPO) is an enzyme, which functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly by myeloid progenitor cell types and neutrophils MPO is released into vascular lumen during inflammation, where it may adhere and internalize the endothelial cells coating vascular walls. Here we describe the moonlighting properties of MPO and its regulation of gene transcription in endothelial cells upon nuclear internalization. We show that MPO independently of its enzymatic activity possess chromatin binding properties in vitro and in cyto. Upon nuclear translocation, MPO changes chromatin condensation. Locally at sites of binding, MPO drives de-condensation of chromatin and at the regions flanking MPO binding sites drives an increased chromatin condensation. MPO-guided changes in chromatin condensation lead to activation of endothelial-to-mesenchymal transition in ECs and enhanced migratory potential. Moreover, MPO directly binds to the double-stranded RNA binding protein and transcription factor ILF3 and facilitates translocation of its isoform NF90 into the nucleus. This results in positive regulation of expression of VEGFA, as well lowered stability of CXCL1 and CXCL8 transcripts due to loss of cytoplasmic ILF3.
2023-05-03 | GSE202860 | GEO
Project description:Previous studies showed that S100A8 and S100A9 are involved in neovascularization as well as in tumor development. At high concentrations, S100A8 and S100A9 cause inflammatory response or apoptosis mediated damage in vascular endothelial cells. But the effect of low concentrations of such proteins on endothelial cells remains unknown. This assay was performed to screen for genes that are involved in the response of Human Unbilican Vascular Endothelial Cells to low concentrations of S100A8. Human Umblical Vascular Endothelial Cells (HUVEC) were cultuered and treated with 10ug/mL S100A8 proteins for 4 or 24 hours. Gene profiling was carried out using two-color microarray. Two-condition experiment, S100A8 treatment vs. non-treatment. Two time points: 4 hours and 24 hours. Biological replicates at each time point: 3 control replicates, 3 treatment replicates.
2011-11-20 | E-GEOD-33768 | biostudies-arrayexpress
Project description:Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids.
2018-08-01 | GSE89475 | GEO
Project description:Myeloperoxidase (MPO) is an enzyme, which functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly by myeloid progenitor cell types and neutrophils MPO is released into vascular lumen during inflammation, where it may adhere and internalize the endothelial cells coating vascular walls. Here we describe the moonlighting properties of MPO and its regulation of gene transcription in endothelial cells upon nuclear internalization. We show that MPO independently of its enzymatic activity possess chromatin binding properties in vitro and in cyto. Upon nuclear translocation, MPO changes chromatin condensation. Locally at sites of binding, MPO drives de-condensation of chromatin and at the regions flanking MPO binding sites drives an increased chromatin condensation. MPO-guided changes in chromatin condensation lead to activation of endothelial-to-mesenchymal transition in ECs and enhanced migratory potential. Moreover, MPO directly binds to the double-stranded RNA binding protein and transcription factor ILF3 and facilitates translocation of its isoform NF90 into the nucleus. This results in positive regulation of expression of VEGFA, as well lowered stability of CXCL1 and CXCL8 transcripts due to loss of cytoplasmic ILF3.
2023-05-03 | GSE202014 | GEO
Project description:Myeloperoxidase (MPO) is an enzyme, which functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly by myeloid progenitor cell types and neutrophils MPO is released into vascular lumen during inflammation, where it may adhere and internalize the endothelial cells coating vascular walls. Here we describe the moonlighting properties of MPO and its regulation of gene transcription in endothelial cells upon nuclear internalization. We show that MPO independently of its enzymatic activity possess chromatin binding properties in vitro and in cyto. Upon nuclear translocation, MPO changes chromatin condensation. Locally at sites of binding, MPO drives de-condensation of chromatin and at the regions flanking MPO binding sites drives an increased chromatin condensation. MPO-guided changes in chromatin condensation lead to activation of endothelial-to-mesenchymal transition in ECs and enhanced migratory potential. Moreover, MPO directly binds to the double-stranded RNA binding protein and transcription factor ILF3 and facilitates translocation of its isoform NF90 into the nucleus. This results in positive regulation of expression of VEGFA, as well lowered stability of CXCL1 and CXCL8 transcripts due to loss of cytoplasmic ILF3.
2023-05-03 | GSE202013 | GEO
Project description:Obesity causes diabetes type 2 (DMT2) leading to vascular dysfunction and finally renal end-organ damage. Vascular smooth muscle (VSM) EGF receptor (EGFR) modulates vascular wall homeostasis in part via serum response factor (SRF), a major regulator of VSM differentiation and a sensor for glucose. We investigated the role of VSM-EGFR during obesity-induced renovascular dysfunction and the EGFR-hyperglycemia crosstalk.
2020-03-01 | GSE144838 | GEO