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Transcriptional adaptations of HUVECs exposed to high and low fluid shear stress

ABSTRACT: The goal of this study was to identify gene signatures in HUVECs exposed to atheroprone low laminar shear stress (LSS) or atheroprotective high laminar shear stress (HSS). The obtained data was used to verify that HSS and LSS application induces gene expression patterns similar to more complex pulsatile and oscillatory flow, respectively.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211662 | GEO | 2022/08/19

REPOSITORIES: GEO

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Integrated Proteomics and Metabolomics Analysis Reveals Differential Lipid Metabolism in HUVEC under high and low shear stress

Project description:<div><b>OBJECTIVE:</b> Atherosclerotic plaque development is closely associated with the hemodynamic forces applied to endothelial cells (EC). Among these, shear stress (SS) plays a key role in disease development since changes in flow intensity and direction could stimulate an atheroprone or atheroprotective phenotype. EC under low or oscillatory SS (LSS) shows upregulation of inflammatory, adhesion and cellular permeability molecules. On the contrary, cells under high or laminar SS (HSS) increase their expression of protective and anti-inflammatory factors. The mechanism behind SS regulation of an atheroprotective phenotype is not completely elucidated.</div><div><b>APPROACH and RESULTS:</b> Here we used proteomics and metabolomics to better understand the changes in endothelial cells (HUVECs) under in vitro LSS and HSS that promote an atheroprone or atheroprotective profile and how these modifications can be connected to atherosclerosis development. Our data showed that lipid metabolism, in special cholesterol metabolism, was downregulated in cells under LSS. The LDLR showed significant alterations both at the quantitative expression level, as well as regarding post-translational modifications. Under LSS, LDLR was seen at lower concentrations and with a different glycosylation profile. Finally, modulating LDLR with atorvastatin led to the recapitulation of a HSS metabolic phenotype in EC under LSS.</div><div><b>CONCLUSIONS:</b> Altogether, our data suggest that there is significant modulation of lipid metabolism in endothelial cells under different SS intensities and that this could contribute to the atheroprone phenotype of LSS. Statin treatment was able to partially recover the protective profile of these cells.</div>

2019-07-25 | MTBLS739 | MetaboLights

Histone Modifications and Chromatin Accessibility in Endothelial Cells under Shear Stress (ChIP-seq)

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.

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Histone Modifications and Chromatin Accessibility in Endothelial Cells under Shear Stress (ATAC-seq)

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Time series RNA profiling of endotheilal cells in response to atheroprone and atheroprotective flows

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

Longitudinal Transcriptional Response of Endothelial Cells to Shear Stress

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.

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HUVECs cultured under normal or high laminar shear stress

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

HUVECs cultured under normal or high laminar shear stress

2011-02-01 | GSE23289 | GEO

CircRNA profiling in laminar shear stress-treated human umbilical vein endothelial cells.

Project description:Laminar shear stress (LSS) suppresses endothelial inflammation and protects the arteries from atherosclerosis. Circular RNAs (circRNAs) are powerful regulators of vascular homeostasis and atherosclerosis; however, their roles in mediating the effects of LSS remain unexplored. To identify the changes in circRNA expression patterns after shear stress stimulation, we conducted circRNA microarray analysis using RNA extracted from HUVECs cultured for 24 h under static or LSS conditions.

2023-09-29 | GSE228636 | GEO

Longitudinal shear stress response in human aortic endothelial cells to atheroprone and atheroprotective conditions

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.

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Effect of shear stress on Chromatin structure

Project description:This study aimed to investigate chromatin accessibility in endothelial cells under pulsatile shear stress (PS) and Oscillatory shear stress (OS). The ATACseq signals were measured at four-time points (0, 2, 8, and 16 hr) under PS or OS. Three replicates were used for each condition and time point.

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