Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from Human Microvascular Endothelial Cells exposed or not to low-dose ionizing radiation

ABSTRACT: We have previously shown that low doses of ionizing radiation (LDIR) induce angiogenesis. In the present study we investigated their action in experimentally induced hindlimb ischemia. We demonstrated that 0.3 Gy, administered for four consecutive days, significantly improves blood perfusion in the murine ischemic limb by stimulating angiogenesis and arteriogenesis. This is achieved through durable and simultaneous up-regulation of a repertoire of pro-angiogenic factors and their receptors in endothelial cells, as evident in cells isolated from the irradiated gastrocnemius muscles. Moreover, we demonstrated that this mechanism is mediated via VEGFR signaling, since VEGFR inhibition abrogated the LDIR-mediated gene up-regulation and impeded the increase in vessel density. Importantly, the vasculature in an irradiated non-ischemic bed is not affected and no adverse effects associated to the use of LDIR were seen. These findings disclose an innovative, non-invasive strategy to induce therapeutic angiogenesis in a murine model of severe hindlimb ischemia, emerging as a novel approach in the treatment of Critical Limb Ischemia patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73341 | GEO | 2017/05/22

SECONDARY ACCESSION(S): PRJNA296712

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Proteomic analysis of vascular tissue from critical limb ischemia mouse models treated with Etrinabdione

Project description:Vasculogenic therapies have been investigated for the treatment of peripheral artery disease (PAD) with very limited success in clinical trials. The isoform PP2A (protein phosphatase 2)/B55alpha inhibits the activity of the prolyl hydroxylase 2 (PHD2) and activates the hypoxia inducing factor-1alpha (HIF-1alpha), playing a key role in in vessel remodeling. Thus, PP2A/B55alpha activators may have the potential to induce angiogenesis and arteriogenesis. Herein we investigated the pharmacological attributes of VCE-004.8 (Etrinabdione) and its effectiveness in a murine model of critical limb ischemia.

2024-04-03 | PXD050360 | Pride

Genome-wide transcriptional alterations during vascular growth in skeletal muscles of type 2 diabetic mice in response to femoral artery ligation

Project description:Diabetes is a major risk factor of cardiovascular disease including coronary and peripheral arterial disease, attributed to impaired arteriogenesis and angiogenesis. Mechanisms behind them are poorly understood due to the complexity of these processes in presence of diabetes. To understand the cellular and molecular mechanisms underlying impaired adaptive vascular responses in type 2 diabetic (T2DM) mouse models of hindlimb ischemia using Genome-wide mRNA sequencing.In response to FAL, collateral density and lumen area were significantly reduced in adductor muscles of T2DM mice at day 7 and 14 days post-FAL. mRNA sequencing suggested an altered gene expression typical for monocyte and macrophage (Mϕ) subsets. Similarly, gene expressions typical of dendritic cell and lymphocyte were altered in adductor muscles of T2DM mice. Ischemic muscles of T2DM mice displayed impaired angiogenesis as revealed by endothelial staining. mRNA sequencing suggested downregulation of crucial genes implicated in angiogenesis and differential expression of genes typical for Mϕ subsets. Immunohistochemistry analysis corroborated with the mRNA sequencing analysis, suggesting an altered Mϕ polarization behind the impaired arteriogenesis and angiogenesis seen in T2DM mouse models of hindlimb ischemia.

2023-01-30 | GSE69123 | GEO

E-Selectin/AAV2/2 Gene Therapy Alters Angiogenesis and Inflammatory Gene Profiles in Mouse Gangrene Model [Inflammation]

Project description:For patients with chronic limb-threatening ischemia and limited revascularization options, alternate means for therapeutic angiogenesis and limb salvage are needed. E-selectin is a cell adhesion molecule that is critical for inflammation and neovascularization in areas of wound healing and ischemia. Here, we tested the efficacy of modifying ischemic limb tissue by intramuscular administration of E-selectin/AAV2/2 (adeno-associated virus serotype 2/2) to modulate angiogenic and inflammatory responses in a murine hindlimb gangrene model. Limb appearance, reperfusion, and functional recovery were assessed for 3 weeks after induction of ischemia. Mice receiving E-selectin/AAV2/2 gene therapy had reduced gangrene severity, increased limb and footpad perfusion, enhanced recruitment of endothelial progenitor cells, and improved performance on treadmill testing compared to control group. Histologically, E-selectin/AAV2/2 gene therapy was associated with increased vascularity and preserved myofiber integrity. E-selectin/AAV2/2 gene therapy also upregulated a panel of pro-angiogenic genes yet downregulated another group of genes associated with the inflammatory response. This novel gene therapy did not induce adverse effects on coagulability, or hematologic, hepatic, and renal function. Our findings highlight the potential of E-selectin/AAV2/2 gene therapy for improving limb perfusion and function in patients with chronic limb-threatening ischemia.

2022-04-29 | GSE201479 | GEO

E-Selectin/AAV2/2 Gene Therapy Alters Angiogenesis and Inflammatory Gene Profiles in Mouse Gangrene Model [Angiogenesis]

2022-04-29 | GSE201476 | GEO

Identification of the initial molecular changes in response to Circulating Angiogenic Cells-mediated therapy in Critical Limb Ischemia

Project description:Circulating angiogenic cells (CACs) constitute promising candidates for cell therapy in critical limb ischemia (CLI) due to their assigned vascular regenerative properties. A label free MS-based quantitative approach was performed to identify protein changes related. We analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissue.

2020-05-27 | PXD017661 | Pride

Effect of neurotrophin p75 receptor (p75NTR) on angiogenesis

Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis Two series of 4 mice each were treated with either control adenovirus (AdNull) or adenovirus expressing neurotrophin p75 receptor (AdP75). Anaesthetized mice received 3 adenovirus injections (for a total of 109 p.f.u. virus in 20 micro L) into 3 equidistant sites of the normoperfused or ischemic left adductor muscles, as described (2. Emanueli C, Graiani G, Salis MB, Gadau S, Desortes E, Madeddu P. Prophylactic gene therapy with human tissue kallikrein ameliorates limb ischemia recovery in type 1 diabetic mice. Diabetes. 2004 Apr;53(4):1096-103. )

2010-06-25 | E-GEOD-9910 | biostudies-arrayexpress

tRNA-Derived Small Non-Coding RNAs in Response to Ischemia Inhibit Angiogenesis

Project description:Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs was strikingly up-regulated in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, the overexpression of tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Our results indicate that tRNA-derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells. Examine small RNAs involved in post-ischemia angiogenesis

2016-03-16 | E-GEOD-70473 | biostudies-arrayexpress

Impaired revascularization in a mouse model of diabetes associated with dysregulation of angiogenic-regulatory network.

Project description:Diabetes is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis or increased endothelial cell apoptosis. Here is it shown that angiogenic repair of ischemic hind limbs was impaired in Lepr db/db mice, a leptin receptor deficient model of diabetes, compared to wild-type C57BL/6 (WT) mice as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hind limb cDNA expression profiles were created from adductor muscle of Lepr db/db and WT mice before and after hind limb ischemia using Affymetrix GeneChip® Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis related proteins were altered in Lepr db/db versus WT mice following ischemic injury. These transcripts included neuropilin-1, VEGF-A, placental growth factor, elastin and matrix metalloproteinases that are implicated in blood vessel growth and maintenance of vessel wall integrity. These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network. Keywords: Diabetes, ischemia, angiogenesis, microarrays

2014-06-30 | GSE3313 | GEO

Effect of neurotrophin p75 receptor (p75NTR) on angiogenesis

2008-07-17 | GSE9910 | GEO

A novel model of chronic limb ischemia with translational significance enables proper evaluation of therapeutic angiogenesis

Project description:We aimed to develop a novel chronic and severe hindlimb ischemia mice model to properly evaluate the therapeutic effects of drug candidates in translational research for critical limb ischemia treatments. We used microarray to compare the gene expression patterns of gastrocnemius muscles at 1st week and 9th week after hindlimb ischemia model operation.

2020-06-10 | GSE152139 | GEO

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