Influence of endothelial Cx40 under atheroprone and atheroprotective flow
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ABSTRACT:
PROVIDER: PRJNA486531 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7706490.fastq.gz | Fastqsanger.gz | |||
| SRR7706500.fastq.gz | Fastqsanger.gz | |||
| SRR7706491.fastq.gz | Fastqsanger.gz | |||
| SRR7706501.fastq.gz | Fastqsanger.gz | |||
| SRR7706492.fastq.gz | Fastqsanger.gz |
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Project description:Atherosclerosis is a focal disease that preferentially develop in the regions of atheroprone disturbed flow, but less in regions of atheroprotective laminar flow. The mechanisms by which atheroprotective laminar flow prevents atherosclerosis at the epigenetic level remain largely unknown. In this study, we observed that laminar flow decreased histone methyltransferase EZH2, which imposes a repressive epigenetic mark of histone 3 lysine 27 trimethylation (H3K27me3) onto target gene promoters, leading to transcriptional silencing. To evaluate the effect of atheroprotective flow on EZH2 and H3K27me3 dependent genome-wide transcriptional profile, we performed RNA-sequencing study on laminar flow and EZH2 siRNA treated human endothelial cells. Venn diagram was used to compare the common regulated genes by both laminar flow and EZH2 depletion. We found atheroprotective flow and EZH2 depletion altere endothelial gene landscape, which include upregulating atheroprotective genes while downregulating pro-atherosclerotic genes.
2017-09-30 | GSE87534 | GEO
Project description:High laminar shear stress (HLSS), as observed in straight parts of arteries, assures a quiescent non-activated endothelium through the induction of the Krüppel-like transcription factors KLF2 and KLF4. Cx40-mediated gap junctional communication contributes to a healthy endothelium by propagating adenosine-evoked anti-inflammatory signals between endothelial cells. As the promoter of the Cx40 gene contains KLF consensus binding sites, we hypothesize that HLSS through the modulation of KLF4, may affect Cx40 expression in ECs, which may affect the quiescent non-activated state of the endothelium.
2019-10-24 | GSE118717 | GEO
Project description:To profile shear stress-regulated endothelial transcriptomes, we performed RNA-seq with HUVECs subjected to different shear flow conditions, including atheroprotective pulsatile shear (PS, 12±4 dyn/cm2) and atheroprone oscillatory shear (OS, 0.5±4 dyn/cm2), or kept as static control (ST) for four time periods (1, 4, 12 and 24 hours)
2017-05-22 | GSE92506 | GEO
Project description:The goal of this study was to find longitudinal transcriptional response of human aortic endothelial cells (HAECs) to pulsatile shear (PS) and oscillatory shear (OS) and compare them with the responses in human umbilical vein endothelial cells (HUVECs) [GSE103672]. PS is associated with an atheroprotective endothelial phenotype, while OS is associated with an atheroprone endothelial phenotype. Using RNASeq method (single-ended 75-bp sequencing on Illumina Hi-seq 4000 instrument), we measured the transcriptional response at 3 time-points (1, 4, and 24 hrs) under PS and OS conditions. Measurements were also taken under static condition (ST, no flow) at t = 0 hr. Three replicates were used for each condition/time-point. Our results indicate that the responses of HAECs and HUVECs are qualitatively similar for endothelial-function relevant genes and several important pathways with a few exceptions, thus demonstrating that HUVECs can be used as a model to investigate the effects of shear on arterial ECs, with some reservations. Our findings show that HAECs exhibit an earlier response or faster kinetics as compared to HUVECs. The comparative analysis in this study offers new insights into the mechanisms of common and disparate stress responses across these two endothelial cell types.
2021-01-13 | GSE160611 | GEO
Project description:Objective - When endothelium is cultured in wells swirled on an orbital shaker, cells at the well centre experience putatively proatherogenic flow whereas those near the edge experience putatively atheroprotective flow. Transcellular transport is decreased equally in both regions, consistent with it being reduced by a mediator released from cells in one part of the well and mixed in the swirling medium. Here we identify the mediator and the flow characteristics that stimulate its release. Approach and Results - Medium conditioned by cells swirled at the edge, but not by cells swirled at the centre or cultured under static conditions, significantly reduced transendothelial transport of a low density lipoprotein (LDL)-sized tracer. Mass spectrometry identified follistatin-like 1 (FSTL1) as a candidate mediator. Cells from the swirled edge produced more FSTL1 than cells from the swirled centre or from static wells. Exogenous FSTL1 reduced transendothelial transport of the LDL-sized tracer and of LDL itself. An inhibitor of transcytosis similarly inhibited tracer transport. Exogenous FSTL1 and medium conditioned by cells swirled at the well edge also inhibited TNF-α-induced VCAM-1 and ICAM-1 expression, phosphorylation of IκBα, nuclear translocation of NF-κB, and monocyte adhesion. Conclusions - Putatively atheroprotective flow stimulates production of FSTL1 from cultured endothelial cells. FSTL1 reduces transcellular transport of LDL-sized particles and of LDL itself, and inhibits endothelial activation. If this also occurs in vivo, it may account for the atheroprotective nature of such flow. The identification of a mediator linking flow to LDL transport suggests novel therapeutic strategies.
2021-08-23 | PXD022068 | Pride
Project description:Longitudinal shear stress response in human aortic endothelial cells to atheroprone and atheroprotective conditions
| PRJNA673729 | ENA
Project description:In order to simulate the effects of shear stress in regions of the vasculature prone to developing atherosclerosis, we subjected human umbilical vein endothelial cells to reversing shear stress, in order to mimic hemodynamic conditions at the wall of the carotid sinus, a site of complex, reversing blood flow and commonly observed atherosclerosis. We compared the effects of reversing shear stress (time-average 1 dyne/cm2, maximum +11 dynes/cm2, minimum -11 dynes/cm2, 1 Hz), arterial steady shear stress (15 dynes/cm2), and low steady shear stress (1 dyne/cm2) in terms of gene expression, cell proliferation, and monocyte adhesiveness. Microarray analysis revealed most differentially expressed genes were similarly regulated by all three shear stress regimens when compared to static culture. Comparisons of the three shear stress regimens to each other allowed identification of 138 genes regulated by low average shear stress and 22 by fluid reversal. Functional assays indicated that low average shear stress induces increased cell proliferation as compared to high shear stress. Reversing shear stress was the only condition that induced monocyte adhesion. Monocyte adhesion was partially inhibited by incubation of the endothelial cells with ICAM-1 blocking antibody. Increased surface heparin sulfate proteoglycan expression was observed in cells exposed to reversing shear stress. When these cells were treated with heparinase III monocyte adhesion was significantly reduced. Our results suggest that low steady shear stress is the major impetus for differential gene expression and cell proliferation, while reversing flow regulates monocyte adhesion.
2009-11-16 | GSE16706 | 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 two main blood flow patterns, namely, pulsatile shear (PS) prevalent in straight segments of arteries and oscillatory shear (OS) observed at branch points, are associated with atheroprotective (healthy) and atheroprone (unhealthy) vascular phenotypes, respectively. The effects of blood flow-induced shear stress on endothelial cells (ECs) and vascular health have generally been studied using human umbilical vein endothelial cells (HUVECs). While there are a few studies comparing the differential roles of PS and OS across different types of ECs at a single time point, there is a paucity of studies comparing the temporal responses between different EC types. In the current study, we measured OS and PS transcriptomic responses in human aortic endothelial cells (HAECs) over 24 h and compared these temporal responses of HAECs with our previous findings on HUVECs. The measurements were made at 1, 4, and 24 h in order to capture the responses at early, mid, and late time points after shearing. The results indicate that the responses of HAECs and HUVECs are qualitatively similar for endothelial function-relevant genes and several important pathways with a few exceptions, thus demonstrating that HUVECs can be used as a model to investigate the effects of shear on arterial ECs, with consideration of the differences. Our findings show that HAECs exhibit an earlier response or faster kinetics as compared to HUVECs. The comparative analysis of HAECs and HUVECs presented here offers insights into the mechanisms of common and disparate shear stress responses across these two major endothelial cell types.
| S-EPMC7848718 | biostudies-literature