Longitudinal shear stress response in human aortic endothelial cells to atheroprone and atheroprotective conditions
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ABSTRACT: 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.
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)
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.
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.
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.
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.
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.
Project description:While variations in gene transcription networks in models of atherosclerosis have been reported, the underlying changes in the chromatin landscape induced by pro-atherogenic stimuli remain elusive. In the present study, we report changes in chromatin regulatory elements that mediate transcriptional control upon the application of oscillatory shear stress of ±3 dyn/cm2 in primary cultured human umbilical vein endothelial cells (HUVECs) at 6 h time point of oscillatory shear stress stimulation compared to static condition.