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Arteriolargenesis can be induced by concomitant stimulation of Nitric Oxide (NO)-Angiopoietin receptor (Tie)-Vascular Endothelial Growth Factor (VEGF) signaling in the rat mesentery angiogenesis assay. We hypothesized that the same combination of exogenously added growth factors would have a positive impact on the recovery of blood flow in a model of unilateral hindlimb ischemia. NO-Tie mice had faster blood flow recovery compared to control mice, as assessed by laser speckle imaging. There was no change in capillary density within the ischemic muscles, but arteriole density was higher in NO-Tie mice. Surprisingly, NO-Tie-VEGF mice recovered no differently than control, arteriole density was similar and capillary density was lower. Dll4 is a driver of arterial specification, so we hypothesized that Notch1 expression would be involved in arteriolargenesis. There was a significant upregulation of Notch1 transcripts in NO-Tie-VEGF compared with NO-Tie mice. Using soluble Dll4 (sDll4), we stimulated Notch signaling in the ischemic muscles. NO-Tie-sDll4 mice had significantly increased capillary and arteriole densities, but impaired blood flow recovery. These results suggest that early Dll4 activation can lead to unproductive angiogenesis and arteriolargenesis, despite increased vascular densities. These results suggest spatial and temporal balance of growth factors needs to be perfected for functional revascularisation. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Microcirculation (New York, N.Y. : 1994)
During CD8+ T cell response, Notch signaling controls short-lived-effector-cell (SLEC) generation, but the exact mechanisms by which it does so remains unclear. The Notch signaling pathway can act as ...
Notch is a transmembrane receptor that mediates intercellular signaling through a conserved signaling cascade in all animal species. Transcriptional and posttranscriptional regulation of Notch recepto...
Most cells in our body communicate during development and throughout life via Notch receptors and their ligands. Notch receptors relay information from the cell surface to the genome via a very simple...
Notch signaling pathway facilitates important cellular functions of the host. Notch signal is essential for the development of T cells, and the role of Notch in fine tuning of αβ versus γδ T cell ...
Notch signaling is conserved in most multicellular organisms and plays critical roles during animal development. The core components and major signal transduction mechanism of Notch signaling have bee...
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other a...
Scapular notch can be reduced by using bigger glenospheres but in some patients it cannot be implanted because of small size. If small size of glenosphere is used then scapular notch may i...
The objective of this phase 1 study is to evaluate the safety and tolerability of Notch Inhibitor in patients with advanced cancer. This study includes dose escalation and dose confirmati...
Background:Altered Toll-like receptor (TLR) expression levels and/or mutations in its signaling pathway (such as MyD88 mutation) contribute to the pathogenesis of lymphoproliferative disor...
A Notch signalling pathway inhibitor study in pediatric and adult patients with relapsed (worsening) or refractory (not responding to treatment) T-cell acute lymphoblastic leukemia/lymphom...
A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. It cleaves several other CELL SURFACE PROTEINS, including INTERLEUKIN-1 RECEPTOR TYPE II; TRANSFORMING GROWTH FACTOR ALPHA; L-SELECTIN; MUCIN-1; and AMYLOID BETA-PROTEIN PRECURSOR. It can also function as an activator of the Notch signaling pathway by mediating the cleavage of NOTCH RECEPTORS.
Microsurgical revascularization to improve intracranial circulation. It usually involves joining the extracranial circulation to the intracranial circulation but may include extracranial revascularization (e.g., subclavian-vertebral artery bypass, subclavian-external carotid artery bypass). It is performed by joining two arteries (direct anastomosis or use of graft) or by free autologous transplantation of highly vascularized tissue to the surface of the brain.
A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.
An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity. This can be a drug or biochemical substance or a cell in an organism or organic sample. ...
Vascular relates to blood vessels (Oxford Medical Dictionary) and can be used to describe the supply of blood, a disease affecting the blood vessels or molecules associated with these structures. For example, <!--LGfEGNT2Lhm-->atherosclerosis ...