Flow-Mediated Modulation of the Endothelial Cell Lipidome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1107180 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28879524.fastq.gz | Fastqsanger.gz | |||
| SRR28879525.fastq.gz | Fastqsanger.gz | |||
| SRR28879526.fastq.gz | Fastqsanger.gz | |||
| SRR28879527.fastq.gz | Fastqsanger.gz | |||
| SRR28879528.fastq.gz | Fastqsanger.gz |
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Project description:The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. In this study, human aortic endothelial cells (HAECs) were exposed to unidirectional laminar flow (20 dynes/cm2) or disturbed flow (±4 dynes/cm2, 2 Hz) for 48 hrs and then subjected to RNA sequencing. The sequencing data was used to analyze changes in endothelial cell gene expression and pathways associated with lipid metabolism.
2024-07-01 | GSE266437 | GEO
Project description:The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 h. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 h. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.
| S-EPMC11307263 | biostudies-literature
Project description:Under pressure: altered endothelial flow response.
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Project description:Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses are not fully understood. Specifically, the role of hydrostatic pressure in the context of flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow. Our study demonstrates that elevated pressure conditions significantly modify shear-induced flow alignment and increase endothelial cell density, a phenomenon often observed in vascular diseases. Utilizing both bulk and single-cell RNA sequencing, we found that while flow is the primary driver of transcriptional changes from static conditions, pressure distinctly modulates this flow response by upregulating gene sets linked to arterial cell phenotypes. Conserved pressure-responsive transcriptional signatures identified in human ECs were upregulated during the onset of circulation in early mouse embryonic vascular development, where pressure was notably associated with transcriptional programs essential to arterial and hemogenic EC fates. Our findings emphasize the necessity of an integrative approach to endothelial cell mechanotransduction, one that encompasses the effects induced by pressure alongside other hemodynamic forces.
2024-03-12 | GSE261063 | GEO
Project description:Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow are primarily mediated by the elevation of transcription factors Krüppel-like factors 2 and 4 (KLF2 and KLF4). Notably, turbulent flow patterns, which predispose to atherosclerosis, significantly reduce the endothelial expression of KLF2 and KLF4 and reulting changes in the transcriptome that exacerbate inflammation and thrombosis. The CCM complex, comprising KRIT1, CCM2, and CCM3 suppress expression of KLF2 and KLF4. Loss of function of the CCM complex has recently been suggested to protect from coronary atherosclerosis in humans. We thus hypothesized that silencing of KRIT1, the central scaffold of the CCM complex, can normalize the effects of turbulent flow on the human endothelial transcriptome. We conducted bulk RNA sequencing (RNA-seq) on human umbilical vein endothelial cells (HUVECs) after silencing KRIT1 expression using specific siRNAs. The endothelial cells were exposed to pulsatile shear stress (laminar flow), oscillatory shear stress (disturbed flow), or no flow for 24 hours.
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Project description:Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We experimentally tuned flow profiles in vitro (microfluidics) and in vivo (zebrafish) and demonstrated that efficient uptake of tEVs occurs in endothelial cells subjected to capillary-like hemodynamics. Such flow profiles partially reroute internalized tEVs towards non-acidic and non-degradative Rab14-positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro-angiogenic transcription factors in flow-stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that capillary-like flow profiles potentiate the pro-tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre-metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics. This set of experiments represents RNAseq of HUVEC cells subjected to 400 µm/s flow versus no flow (static conditon).
2023-07-11 | E-MTAB-13156 | biostudies-arrayexpress
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.
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Project description:Rocking-platform perfusion systems rely on hydrostatic pressure differences to perfuse cells in organ-on-chip devices. These systems are popular due to their tubing-free design, which facilitates parallelization, an essential feature for drug discovery, precision medicine, and academic research. However, most of these systems generate bidirectional flow, which does not accurately replicate the physiological conditions experienced by endothelial cells (ECs) in the microvasculature. To address this limitation, pump-based systems are often employed to generate unidirectional flow, though they require external tubing, thereby limiting scalability compared to rocking platforms. In this study, we compared the transcriptomic responses of endothelial cells exposed to flow generated either by a rocking platform or a peristaltic pump, under matched average flow rates. Our results revealed distinct transcriptomic profiles induced by the two flow modalities, with hundreds of genes differentially expressed between the two conditions. After 4 hours of flow exposure, we observed an enrichment in signaling pathways including NF-κB, ERK, BMP and MAPK. Furthermore, after 24 hours of flow exposure, we identified significant changes in the genes involved in biological processes such as immune cell migration, angiogenesis and vascular and extracellular matrix remodeling, highlighting how different flow generated by pump or rokcer can shape endothelial cell behavior at the molecular level.
2025-07-28 | GSE272273 | 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.
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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).
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