Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Improving blood vessel function in peripheral artery disease: endothelial-derived TRAIL generates stable microvessels in ischemia via TRAIL-R2

ABSTRACT: Ischemia reduction in peripheral artery disease (PAD) through angiogenesis requires endothelial cell (EC) and pericyte interactions to form stable microvascular networks, but processes mediating this are disrupted in PAD. Patients with cardiovascular disease have suppressed levels of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). The contribution of endothelial cell (EC)-derived TRAIL to generating stable blood vessel networks and the impact of its receptors in PAD is unknown.We used scRNA-seq to identify molecular determinants that are altered in ischemic tissues of EC-specifc TRAIL KO mice vs littremate control mice, specifically looking at EC-pericyte interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE242268 | GEO | 2024/08/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Breast tumors interfere with endothelial TRAIL at the pre-metastatic niche to promote cancer cell seeding

Project description:Purpose: To study the effects of endothelial cell (EC)-specific TRAIL depletion on lung endothelial cells. Here, we used RNA sequencing to explore the transcriptional changes of lung ECs upon deletion of TRAIL specifically in ECs. RNA from 2.000.000 sorted lung ECs (viability dye- CD45- CD31+) from EC-specific TRAIL WT and KO mice (Cdh5.iCreERT2xTnfsf10Lox/Lox) were isolated and the concentration as well as purity was determined spectrophotometrically using the Nanodrop ND-1000 (Nanodrop Technologies). Per sample, an amount of 3000ng of total RNA was used as input. Subsequently, preparation was performed with KAPA stranded mRNA seq according to the protocol and samples were pooled equimolar. Sequencing was performed as single end of 50bp on hiseq 4000 from Illumina. 35-40 Million reads were generated per sample. Raw FASTQ reads were mapped using STAR v2.7.1a and gene reads counts were estimated by RSEM v1.2.28 using GENCODE reference annotation of the mouse genome (GRCm38), version M24 (Ensembl 99). Gene reads counts were estimated by RSEM using GENCODE reference annotation of the mouse genome (GRCm38), version M24 (Ensembl 99). Differential expression of EC-specific TRAIL KO (EC-Tg/W) vs control (EC-W/W) was performed using the DESeq2 R package (v1.26.0). The significance was determined by padj < 0,05. The gene set enrichment analysis (GSEA) was performed using the pre-ranked gene list by log2 fold-change (EC-Tg/W vs EC-W/W control) and the MSigDB gene sets. Only gene sets containing between 5 and 500 genes were retained and the number of permutations was set at 1000.

2023-04-13 | GSE199461 | GEO

microRNA expression of TRAIL-sensitive and TRAIL-resistant Bel-7402 cells

Project description:To further analyze the change of microRNA (miRNA) between TRAIL-sensitive and TRAIL-resistant Bel-7402 cells Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

2015-10-20 | GSE74130 | GEO

Suppression of ANGPTL4 Reprograms Endothelial Cell Metabolism and Inhibits Angiogenesis

Project description:Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.

2023-11-22 | GSE211128 | GEO

TRAIL expressing monocyte/macrophages reduce inflammation and attenuate atherosclerosis

Project description:Circulating TRAIL is reduced in cardiovascular disease patients and TRAIL deletion in mice exacerbates disease. The source of TRAIL and protective mechanism(s) are unclear. Monocyte TRAIL mRNA was reduced from coronary artery disease patients, strikingly associating with reduced plasma TRAIL. A strong inverse correlation between plasma TRAIL and IL-18 was observed, with IL-18 repressing monocyte TRAIL mRNA. In mice, two sources were investigated using bone-marrow (BM) transplants; TRAIL expressed only in BM (BM-TRAIL) or everywhere except BM (parenchymal-TRAIL), vs. whole-body TRAIL ablation (null-TRAIL). BM-TRAIL attenuated macrophage content and atherosclerosis. BM-derived macrophages with TRAIL deletion were more inflammatory, with impaired migration and reduced expression of cholesterol efflux, efferocytosis and nitric oxide-controlling genes. TRAIL expression also reduced islet macrophage content, but only parenchymal-TRAIL islets had improved function. Recombinant TRAIL administration stimulated insulin expression and islet mass. We propose TRAIL maintains monocyte/macrophage homeostasis and limits the progression of atherosclerosis and islet dysfunction.

2019-12-03 | GSE107645 | GEO

Comparison of Trail+/+ versus Trail-/- splenic NK cells from naïve and LCMV-infected mice

Project description:Investigation of the change of the Trail-dependent NK cell transcriptome during short-term (24h) infection with lymphocytic choriomeningitis virus (LCMV). RNA sequencing-based transcriptomics analysis was performed in spleen-isolated (NK1.1+CD3-) NK cells from 3 naïve Trail+/+ mice, 3 naive Trail-/- mice, 4 LCMV-infected Trail+/+ mice, and 4 LCMV-infected Trail-/- mice.

2019-08-27 | E-MTAB-7562 | biostudies-arrayexpress

TRAIL Is a Novel Antiviral Protein against Dengue Virus

Project description:Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. To shed light on mechanisms involved in the cellular response to dengue virus (DV), we assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of infected primary human cells and identified changes common to all cells. The common response genes included a set of 23 genes significantly induced upon DV infection of human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes, and B cells (analysis of variance, P < 0.05). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one of the common response genes, was identified as a key link between type I and type II interferon response genes. We found that DV induces TRAIL expression in immune cells and HUVECs at the mRNA and protein levels. The induction of TRAIL expression by DV was found to be dependent on an intact type I interferon signaling pathway. A significant increase in DV RNA accumulation was observed in anti-TRAIL antibody-treated monocytes, B cells, and HUVECs, and, conversely, a decrease in DV RNA was seen in recombinant TRAIL-treated monocytes. Furthermore, recombinant TRAIL inhibited DV titers in DV-infected DCs by an apoptosis-independent mechanism. These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV. We used Affymetrix microarrays to study the response of human host cells to dengue virus (DV). Keywords: virus infection of multiple cell types

2008-01-05 | GSE9378 | GEO

Transcription profiling of human TRAIL-resistant metastatic vs primary TRAIL-sensitive melanoma cells

Project description:T1 and G1 are the two melanoma cell lines, established from primary tumor (T1) and lymph node metastases (G1) of a 77 years old male patient. While G1 cells were resistant to TRAIL (TNF-related apoptosis-inducing ligand) mediated cell death, T1 cells exhibited a high dose- and time-dependent sensitivity to TRAIL. Cells were treated with or without of two doses (0.2 and 1ug/ml) of TRAIL for 24 h. Gene expression of each sample vs pool was measured. TRAIL-resistant metastatic G1 vs primary TRAIL-sensitive T1 was compared.

2006-01-01 | E-MEXP-247 | biostudies-arrayexpress

Proteomic analysis of TRAIL-induced endogenous RIPK3-dependent necrosome complex

Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.

2021-03-18 | PXD003383 | Pride

TRAIL-induced cancer secretome

Project description:To comprehensively determine which factors are secreted by cancer cells upon TRAIL stimulation, we conducted an unbiased mass spectrometric analysis of TRAIL’s secretome in resistant A549 cells.

2017-12-19 | PXD005664 | Pride

Closing the mitochondrial permeability transition pore in hiPSC-derived endothelial cells induces glycocalyx formation and functional maturation.

Project description:Human induced pluripotent stem cells (hiPSCs) are used to study organogenesis and model disease as well as being developed for regenerative medicine. Endothelial cells are among the many cell types differentiated from hiPSC, but their maturation and stabilization fall short of that in adult endothelium. We examined whether shear stress alone or in combination with pericyte co-culture would induce flow alignment and maturation of hiPSC-derived endothelial cells (hiPSC-ECs) but found no effects comparable to those in primary microvascular EC. In addition, hiPSC-ECs lacked a luminal glycocalyx, critical for vasculature homeostasis, shear stress sensing and signalling. We noted however, that hiPSC-EC have dysfunctional mitochondrial permeability transition pores, resulting in reduced mitochondrial function and increased reactive oxygen species (ROS). Closure of these pores by cyclosporine-A improved EC mitochondrial function but also restored the glycocalyx such that alignment to flow took place. These indicated that mitochondrial maturation is required for proper hiPSC-EC functionality.

2019-12-14 | E-MTAB-8392 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data