Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
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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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”
From Endothelial destabilization by angiopoietin-2 via integrin β1 activation (2015) · cites this paper as [6]
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”
From Endothelial destabilization by angiopoietin-2 via integrin β1 activation (2015) · cites this paper as [6]
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).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [27]
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]
In sites of vascular remodeling, Ang-2 can block the action of Ang-1 through competitive inhibition, thereby destabilizing the vessel structure.
“In these regions, Ang-2 can block the action of Ang-1 through competitive inhibition, thereby destabilizing the vessel structure (84)”
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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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