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MRNA expression profile of Tie2 monocytes in limb ischemia patients and controls

ABSTRACT: Tie2-expressing monocytes do not appear to effect revascularisation in critical limb ischemia (CLI) patients, despite a large body of evidence demonstrating their pro-angiogenic potential when isolated from control patients. In order to understand what might cause this loss of angiogenic function, we carried out a whole genome microarray analysis of mRNA isolated from Tie2-expressing monocytes from CLI patients and compared that with age-matched control samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84626 | GEO | 2016/07/21

SECONDARY ACCESSION(S): PRJNA330686

REPOSITORIES: GEO

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mRNA expression profile of Tie2 monocytes in limb ischemia patients and controls

Project description:Tie2-expressing monocytes do not appear to effect revascularisation in critical limb ischemia (CLI) patients, despite a large body of evidence demonstrating their pro-angiogenic potential when isolated from control patients. In order to understand what might cause this loss of angiogenic function, we carried out a whole genome microarray analysis of mRNA isolated from Tie2-expressing monocytes from CLI patients and compared that with age-matched control samples. 12 samples in total

2016-07-21 | E-GEOD-84626 | biostudies-arrayexpress

miRNA expression profiles of TIE2 expressing Monocytes (TEMs)

Project description:To identify the miRNA expressing profiles of TIE2 expressing Monocytes (TEMs), we have employed the Agilent Human miRNA 8×60K (Design ID:046064) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.

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Gene expression profiles of TIE2 expressing Monocytes (TEMs)

Project description:To identify the gene expressing profiles of TIE2 expressing Monocytes(TEMs), we have employed the Agilent lncRNA Gene Expression 4Ã180K(Design ID:042818) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.Expressions of sixteen genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern. The gene expressions of three independent paried TEMs and TIE2- Monocytes samples from different donors were measured.

2017-05-17 | E-GEOD-57783 | biostudies-arrayexpress

Gene expression profiles of TIE2 expressing Monocytes (TEMs)

Project description:To identify the gene expressing profiles of TIE2 expressing Monocytes(TEMs), we have employed the Agilent lncRNA Gene Expression 4×180K(Design ID:042818) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.Expressions of sixteen genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern.

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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

Expression data: Venous malformation-causative TIE2-mutations mediate an AKT-dependent decrease in PDGFB

Project description:Comparison of transcriptional profiles of human umbilical vein endothelial cells (HUVECs) expressing wild-type vs. VM-causative mutant forms of TIE2/TEK. The effects of the most common Venous Malformation-causative mutations in the endothelial cell tyrosine kinase receptor: R849W and L914F, were tested. 743 genes were differentially expressed across the four groups. The 80 genes distinguishing between L914F and wild-type TIE2-expressing HUVECs were analyzed in greater detail. 3 batches each of: non-transfected, and wild-type TIE2, R849W-TIE2, and L914F-TIE2 overexpressing HUVECs were compared by exon-array profiling.

2013-06-04 | E-GEOD-46684 | biostudies-arrayexpress

Expression data: Venous malformation-causative TIE2-mutations mediate an AKT-dependent decrease in PDGFB

2013-06-04 | GSE46684 | GEO

Enhancing Cell-Based Regenerative Therapies with Peptide-Modified Thermo-responsive Citrate-Based Biomaterials for Treatment of Critical Limb Ischemia

Project description:Critical limb ischemia (CLI) poses a significant health challenge, marked by severe morbidity and limited treatment options leading to high mortality rates. Despite the promise of cell-based therapy, challenges such as poor cell survival and engraftment during and after cell delivery hinder its efficacy. This study explores the potential of peptide-modified thermo-responsive citrate-based biomaterials as carriers for endothelial cell delivery to promote vascular regeneration in CLI. Specifically, various pro-survival peptides were covalently tethered to poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to investigate their effect on the delivery of vascular endothelial cells to skeletal muscle tissue. After screening with in vitro and in vivo experiments, laminin-derived peptide A5G81 and VEGF-derived peptide QK were identified to promote endothelial cell spreading, proliferation, and prolonged cell survival when tethered onto PPCN The viscoelastic properties of PPCN provided protection against shear stress induced cell death during injection, while the peptides regulated endothelial cell behavior via distinct molecular pathways. Importantly, intramuscular delivery of endothelial cells with PPCN-A5G81 and PPCN-QK in a murine hindlimb ischemia model resulted in significant improvements in limb perfusion, tissue preservation and functional outcomes. Furthermore, endothelial cell delivery with PPCN-A5G81 and PPCN-QK also promoted positive skeletal muscle remodeling following ischemic injury. These findings underscore the potential of bioactive materials as novel cell delivery carriers for CLI therapy, with implications for advancing regenerative therapeutics and revolutionizing CLI treatment strategies.

2024-04-12 | GSE263721 | GEO

Changes in bone marrow resident monocyte gene expression upon induction of ischemia

Project description:There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such conditioning signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR(-/-) and IL-6(-/-) mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP(-/-) mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes. Bone marrow was harvested from CX3CR1+/GFP heterozygous mice and CX3CR1-GFP+ monocytes were sorted at baseline and at 24 hours post-induction of hindlimb ischemia by femoral artery ligation. Paired samples from three independent experiments were analyzed.

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