RGD Reference Report - Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues. - Rat Genome Database

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Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues.

Authors: Liu, Ren  Trindade, Alexandre  Sun, Zhanfeng  Kumar, Ram  Weaver, Fred A  Krasnoperov, Valery  Naga, Kranthi  Duarte, Antonio  Gill, Parkash S 
Citation: Liu R, etal., Biochem Biophys Res Commun. 2012 Feb 3;418(1):173-9. doi: 10.1016/j.bbrc.2012.01.002. Epub 2012 Jan 9.
RGD ID: 155663358
Pubmed: PMID:22252294   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2012.01.002   (Journal Full-text)

Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ischemia amelioratesISODll4 (Mus musculus)155663358; 155663358 RGD 
ischemia amelioratesIMP 155663358 RGD 
limb ischemia amelioratesISODll4 (Mus musculus)155663358; 155663358 RGD 
limb ischemia amelioratesIMP 155663358 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dll4  (delta like canonical Notch ligand 4)

Genes (Mus musculus)
Dll4  (delta like canonical Notch ligand 4)

Genes (Homo sapiens)
DLL4  (delta like canonical Notch ligand 4)


Additional Information