Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites
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ABSTRACT:
ORGANISM(S): Danio rerio Homo sapiens
PROVIDER: GSE198221 | GEO | 2022/03/14
REPOSITORIES: GEO
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Project description:Many studies have characterised the effect of normal laminar shear stress (LSS) on endothelial responses, however elevated shear stress, as would be experienced overlying a stenotic plaque, has not been studied in depth. Therefore we used transcriptomics and related functional analyses to compare cells exposed to laminar shear stress at 15 or 75 dynes/cm2 for 24 hours (LSS15-normal or LSS75-high shear stress). Human umbilical vein endothelial cells (HUVEC n=4 per flow condition from different batches of pooled donor HUVEC p2) were cultured for 24 hours on gelatin coated slides under laminar shear stress of either 15 dynes/cm2 or 75 dynes/cm2 (LSS15 or LSS75) to assess the effect of high shear stress on endothelial cells. Total RNA was obtained using Qiagen kit and array analysis performed by Service XS (Leiden, Netherlands).
2011-02-01 | E-GEOD-23289 | biostudies-arrayexpress
Project description:Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites
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Project description:Atherosclerosis is an important pathological factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger pathophysiological changes. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi on human endothelial cells in an atherosclerosis in vitro model was investigated using global protein expression profiling. For this purpose, human umbilical cord derived vascular endothelial cells (HUVEC) were treated with TNFα to mimic the inflammatory condition and were exposed to 24h laminar shear stress in the presence or absence of a BRD4 inhibitor, JQ1. Data-independent acquisition mass spectrometry (DIA-MS) alloqed us to quantify 3316 proteins for further statistical analysis. Differentially regulated proteins indicate a clear influence of inflammation and shear stress on human endothelial cells. Overall, application of JQ1 is led to significant changes in the proteome, including a strong anti-inflammatory response as well as a potentially negative impact on atherosclerosis formation. To our knowledge, this is the first proteomics study on HUVEC which investigates the influence of shear stress and BET inhibition in TNFα inflammatory endothelial cell culture model.
2022-10-30 | PXD035842 | Pride
Project description:The mechanisms by which oscillatory shear (OS) induces, while high laminar shear stress (LS) prevents, atherosclerosis are still unclear. Here, we examined the hypothesis that OS induces inflammatory response, a critical atherogenic event, in endothelial cells by a miRNA-dependent mechanism. In particular, miR-663 mediated OS-induced inflammation through monocyte adhesion to endothelial cells. The potential targets of miR-663 were examined by knockdown of miR-663 and then the gene expression profiles were determined under shear stress conditions. To determine the potential targets of miR-663, HUVEC were transfected either with miR-663-LNA (inhibitor of miR-663) or control-LNA and then subjected to OS or LS for 24hr. Total RNA were collected from these four groups and microarray studies (Illumina HumanHT-12 v3 beadchip) were performed.
2011-03-10 | E-GEOD-20739 | biostudies-arrayexpress
Project description:The goal of this study was to find longitudinal transcriptional response of Human Umbilical Vein Endothelial Cells (HUVECs) to pulsatile shear (PS) and oscillatory shear (OS). PS is associated with an atheroprotective endothelial phenotype, while OS is associated with an atheroprone endothelial phenotype. Using RNASeq method (single-ended 50-bp sequencing on Illumina Hi-seq 2000 instrument), we measured the transcriptional response at 10 time-points (1, 2, 3, 4, 6, 9, 12, 16, 20, 24 hr) under PS and OS conditions. Low flow scenario was used as static condition. Two replicates were used for each condition/time-point. Results: Through combining the temporal data on differentially expressed transcription factors and their targets with existing knowledge on relevant functional pathways, we infer the causal relationships between disparate endothelial functions through common transcriptional regulation mechanisms. Our study presents the first comprehensive temporally longitudinal experimental study and mechanistic model of shear stress response. By comparing the relative endothelial expressions of genes between OS and PS, we provide novel insights and an integrated perspective into endothelial cell function in response to differential shear.
2017-10-10 | GSE103672 | GEO
Project description:This data set reveals the changes of histone modifications and chromatin accessibility in human umbilical vein endothelial cells (HUVECs) under atheroprotective pulsatile shear (PS), atheroprone oscillatory shear (OS), or with KLF4 overexpression. Using ChIP-Seq, we defined the H3K27ac and H3K4me1 enrichment under PS and OS conditions. Using ATAC-seq, we identified the chromatin accessibility under KLF4 overexpression.
2020-03-11 | GSE128390 | GEO
Project description:This data set reveals the changes of histone modifications and chromatin accessibility in human umbilical vein endothelial cells (HUVECs) under atheroprotective pulsatile shear (PS), atheroprone oscillatory shear (OS), or with KLF4 overexpression. Using ChIP-Seq, we defined the H3K27ac and H3K4me1 enrichment under PS and OS conditions. Using ATAC-seq, we identified the chromatin accessibility under KLF4 overexpression.
2020-03-11 | GSE128389 | GEO
Project description:The shear stress-induced transcription factor Krüppel-like factor 2 (KLF2) confers anti-inflammatory properties to endothelial cells through inhibition of activator protein 1, presumably by interfering with MAPK cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA micro-array analysis. No gross changes in MAPKs were detected, rather phosphorylation of actin cytoskeleton-associated proteins, including Focal Adhesion Kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH2-terminal kinase (JNK) and its downstream targets ATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, we term shear fibers, which are distinct from thrombin- or TNF-α-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers. Tramscriptome profiling: Three independent isolates of Human Umbilical Vein Endothelial cells were transduced with lentiviral vectors expressing Kruppel Like Factor 2 (KLF2) or no protein (mock), and at time after transduction 24 h, 48 h, 72 h , RNA was isolated and hybridized to GPL4868 microarrays using dye swap procedure Kinome profiling: Two independent isolates of Human Umbilical Vein Endothelial cells were transduced with lentiviral vectors expressing Kruppel Like Factor 2 (KLF2) or no protein (mock), and at time after transduction 72 h , total cellular protein was isolated and hybridized to Kinexus KAM-1.1 phosphoprotein (kinexus) microarrays using dual color procedure in duplicate
2010-06-25 | E-GEOD-19412 | biostudies-arrayexpress
Project description:Laminar shear stress due to constant blood flow is known to play a critical role in maintaining vascular health. In contrast, endothelial cell senescence appears to be closely associated with the incidence of vascular disorder. In an attempt to identify functional biomarkers for age-related vascular health/disease, the present study investigated differential gene expression of young and senescent human umbilical vein endothelial cells (HUVECs) under static and laminar shear stress. We used a cDNA microarray method to compare gene expression profiles of young and senescent HUVECs under static and laminar shear stress conditions. Experiment Overall Design: Senescent cells were prepared by continuous subculture in vitro, and a cone-and-plate device was used to impose laminar shear stress onto cells. Young and senescent cells were exposed to laminar shear stress or maintained under static conditions. Total mRNA was extracted and gene expression profiles were analyzed by cDNA microarray.
2009-06-01 | E-GEOD-13712 | biostudies-arrayexpress
Project description:Laminar shear stress due to constant blood flow is known to play a critical role in maintaining vascular health. In contrast, endothelial cell senescence appears to be closely associated with the incidence of vascular disorder. In an attempt to identify functional biomarkers for age-related vascular health/disease, the present study investigated differential gene expression of young and senescent human umbilical vein endothelial cells (HUVECs) under static and laminar shear stress. We used a cDNA microarray method to compare gene expression profiles of young and senescent HUVECs under static and laminar shear stress conditions. Keywords: stress response, age state analysis
2009-05-23 | GSE13712 | GEO