The effects of primary cilia on endothelial gene expression exposed to flow
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139580 | GEO | 2022/05/25
REPOSITORIES: GEO
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Project description:Wall shear stress (WSS) is proposed to influence intracranial aneurysm growth and rupture. Physiological WSS in cerebral arteries is estimated around 20-30 dynes/cm2. The WSS typically observed in human IAs is close to 2 dynes/cm2 for wide-neck aneurysms with a slow recirculating flow and >70 dynes/cm2 in aneurysms with impinging “jet flow”. In this study, we investigated the effects of aneurysmal low and supra-high WSS on endothelial cells.
2021-11-04 | GSE173928 | GEO
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 study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis. Human umbilical vein endothelial cells (HUVECs) were preconditioned to a unidirectional clockwise shear stress of 15 dynes/cm2 for 24 hours. An acute increase in shear stress magnitude to 30 dynes/cm2 in either a clockwise (non-reversed) or counter-clockwise (reversed) direction was applied for 6 hours. An additional preconditioned control culture was maintained under a unidirectional clockwise shear stress of 15 dynes/cm2 and harvested at the same time point, 6 hours post-conditioning. Each condition of reversed, non-reversed, and control was performed in tandem from the same starting cell culture as one replicate. The total experiment consisted of four replicates. Gene transcription was then assessed using microarray expression analysis.
2016-04-01 | E-GEOD-46248 | biostudies-arrayexpress
Project description:To investigate the function of oscillating shear stress in the regulation of endothelial progenitor cell (EPCs) differentiation, we used EPCs derived from the umbilical cord blood loaded with OSS for 12h. OSS (±3.5 dynes/cm2, 1 Hz frequency) was loaded using a Flexcell flow STR-4000 parallel plate flow chamber system.
2022-08-19 | GSE211402 | GEO
Project description:RNA-seq technology was used to reveal the transcriptome changes of tubular epithelia in response to fluid flow and determine the role of primary cilia in this process. Many fluid flow-sensitive genes were identified, among which are those regulated by primary cilia sensing of fluid flow. These genes were further validated by RT-qPCR.
2018-01-27 | GSE109701 | GEO
Project description:Biomechanical forces influence vascular function, but the molecular mechanisms regulating many of these mechano-activated cellular events remain largely uncharacterized. In particular, the vascular endothelium can sense alterations in hemodynamic shear stress which, in the context of adaptive remodeling or arteriogenesis, has been shown to lead to the generation of endothelial-derived signals critical for controlling blood vessel structure and function. Here, we sought to define the arteriogenic responses evoked in endothelial cells exposed to flow using transciptional profiling. Analysis of these transcriptional programs identified several genes previously shown to be important for endothelial-smooth muscle interactions and vascular remodeling, including the transcription factor kruppel-like factor 2 (KLF2).
2009-01-01 | GSE11583 | GEO
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:Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation.
2012-12-24 | GSE40170 | GEO
Project description:Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. Microarray analysis of two distinct flow pattern regions were identified in the normal rat aorta. Tissue pieces from groups of five animals were pooled for each region giving total of 28 pools; 14 paired sample pools of high and low wall shear stress.
2012-12-24 | E-GEOD-40170 | biostudies-arrayexpress
Project description:The effects of primary cilia on endothelial gene expression exposed to flow
| PRJNA580367 | ENA