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March 2, 1999Proceedings of the National Academy of SciencesOpen Access

Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans

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Population

Mouse and human genomic/cDNA libraries, mouse and human endothelial cells, and mouse fibroblasts.

Design

Preclinical

Authors

DVDavid M. ValenzuelaPolitecnica Salesiana UniversityJGJennifer GriffithsStowers Institute for Medical ResearchJRJosé RojasRegeneron (United States)

Discussion

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Implication

Species-specific angiopoietin functions caution against mouse-to-human extrapolation for Tie2 therapies; leaves open human angiopoietin-4 as a therapeutic target.

Structured PICO

P
Population
Mouse and human genomic/cDNA libraries, mouse and human endothelial cells, and mouse fibroblasts.
I
Intervention
Cloning, expression, and functional characterization of angiopoietin-3 (mouse) and angiopoietin-4 (human).
O
Outcome
Binding to Tie1 and Tie2 receptors, and activation or antagonism of Tie2 receptor phosphorylation.

The identification of angiopoietin-3 and angiopoietin-4 expands the angiopoietin family of vascular endothelial growth factors and highlights their diverging evolutionary functions as a Tie2 antagonist and agonist, respectively.

Limitations

  • Formal proof that native angiopoietin-3 acts as an antagonist awaits production of high enough concentrations of the native ligand.

Cite This Study

Valenzuela et al. (1999) studied this question.

synapsesocial.com/papers/6a7f8efefb3b41a99728bdeahttps://doi.org/10.1073/pnas.96.5.1904
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Also Consider

Synapse has enriched 2 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis1997 · 3,590 citations
  2. 2Signaling Vascular Morphogenesis and Maintenance1997 · 1,202 citations