Cited by 3,570Angiogenesis and VEGF in CancerLymphatic System and DiseasesAxon Guidance and Neuronal Signaling

Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis

Maisonpierre, Peter C., Suri, Chitra, Jones, Pamela F., Bartunkova, Sona, Wiegand, Stanley J., Radziejewski, Czeslaw, Compton, Debra, McClain, Joyce +6 more·1997·Science

Abstract

Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell–specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.

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Crossref · 10.1126/science.277.5322.55

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  • Transgenic expression of Ang2 in mouse embryos induced severe vascular abnormalities, including a discontinuous vascular network and collapsed endocardial lining of the heart.

    “Transgenic expression of Ang2 in mouse embryos induced severe vascular abnormalities, including a discontinuous vascular network and collapsed endocardial lining of the heart6”
  • The vessel discontinuities caused by Ang2 overexpression were more severe than in Ang1 or Tie2 gene-targeted embryos, suggesting that Ang2 may have additional functions besides inhibiting the Ang1-Tie2 signals.

    “However, the vessel discontinuities caused by Ang2 overexpression were more severe than in Ang1 or Tie2 gene-targeted embryos, suggesting that Ang2 may have additional functions besides inhibiting the Ang1–Tie2 signals6”
  • Transgenic overexpression of ANGPT2 in mice leads to aberrant and decreased EC-basement membrane matrix interactions.

    “transgenic overexpression of ANGPT2 in mice leads to aberrant and decreased EC-basement membrane matrix interactions (27, 28).”
  • Both Ang-1 and Ang-2 can bind to the common endothelial cell tyrosine receptor, Tie-2.

    “Both Ang-1 and Ang-2 can bind to the common endothelial cell tyrosine receptor, Tie-2 (83,84)”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [84]

  • Ang-2 is an antagonist for the Tie-2 receptor and is exclusively expressed in sites of vascular remodeling.

    “Ang-2, on the other hand, is an antagonist for the Tie-2 receptor and is exclu-sively expressed in sites of vascular remodeling (83,84,88)”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [84]

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Authors
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., Daly, T. J., Davis, S., Sato, T. N., & Yancopoulos, G. D.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
  • Maisonpierre, Peter C.
  • Suri, Chitra
  • Jones, Pamela F.
  • Bartunkova, Sona
  • Davis, Samuel
  • Sato, Thomas N.
  • Yancopoulos, George D.
Venue
Science
Published
1997-07-04
Volume
277
Issue
5322
Pages
55-60
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2152215024
Cited by
3,570
References
30
Citations by year
2026: 51 · 2025: 60 · 2024: 84 · 2023: 97 · 2022: 74 · 2021: 104 · 2020: 107 · 2019: 84 · 2018: 87 · 2017: 121 · 2016: 113 · 2015: 104 · 2014: 124 · 2013: 125 · 2012: 157
FWCI
35.59
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
angiopoietin-2, angiopoietin-1, Tie2 receptor, angiogenesis, endothelial cells, vascular development, vascular remodeling, transgenic overexpression
MeSH terms
Amino Acid Sequence, Animals, Blood Vessels, Cells, Cultured, Cloning, Molecular, Embryo, Mammalian, Endothelium, Vascular, Female, Humans, Ligands, Lymphokines, Membrane Glycoproteins, Mice, Transgenic, Molecular Sequence Data, Phosphorylation, Proteins, Recombinant Fusion Proteins, Signal Transduction, Endothelial Growth Factors, Rats, Sprague-Dawley, Neovascularization, Physiologic, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Angiopoietin-1, Angiopoietin-2, Receptor, TIE-2, Mice, Rats

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