Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo
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Modulation of Tie2 receptor activity by its angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity. It has been proposed that angiopoietins 1 (Ang1) and 2 (Ang2) are pro- and anti-angiogenic owing to their respective agonist and antagonist signaling action through the Tie2 receptor. The function of Ang2 has remained controversial, however, with recent reports suggesting that in some circumstances, it may be pro-angiogenic. We have examined this issue using the transient ocular microvessel network called the pupillary membrane as a unique in vivo model for studying the effects of vascular regulators. We show that in vivo , in the presence of endogenous vascular endothelial growth factor (VEGF)-A, Ang2 promotes a rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulates sprouting of new blood vessels. By contrast, Ang2 promotes endothelial cell death and vessel regression if the activity of endogenous VEGF is inhibited. These observations support a model for regulation of vascularity where VEGF can convert the consequence of Ang2 stimulation from anti- to pro-angiogenic.
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In the presence of VEGF, Ang-2 can prime vessels to mount a robust pro-angiogenic response.
“in the presence of VEGF, Ang-2 can prime vessels to mount a robust pro-angiogenic response (89)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [89]
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“PDGF-A, NOV, AGN2, and SCG2 are involved in angiogenesis [46-49], whereas ADAM12 and RL play an important role in cell motility, invasion and metastasis [50,51].”
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“In agreement is a recent in vivo study using the pupillary membrane, a transient ocular microvessel network, which shows that following VEGF inhibition, Ang2 promotes endothelial cell death and blood vessel regression.(53) This concept can be extended to the retina, as Ang2-deficient mice have abnormal vascular develo…”
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“Whilst Ang1 supports endothelial cell survival and promotes endothelium integrity,(12) Ang2 by itself antagonizes Ang1 signaling leading to vessel destabilization and regression; however, in combination with VEGF it stimulates new vessel formation.(13) Besides VEGF and the Angs, there are other factors that stimulate…”
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- Authors
- Lobov, I. B., Brooks, P. C., & Lang, R. A.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Lang, Richard A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-08-05
- Volume
- 99
- Issue
- 17
- Pages
- 11205-11210
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC123234
- OpenAlex
- W2113920157
- Semantic Scholar
- 60029f2ec9a0f8c30ad5b2536f206fc2cbab3666
- Cited by
- 676
- References
- 30
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 32 · 2023: 20 · 2022: 31 · 2021: 23 · 2020: 14 · 2019: 24 · 2018: 21 · 2017: 16 · 2016: 25 · 2015: 34 · 2014: 29 · 2013: 37 · 2012: 35
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- International Retinal Research Foundation
- National Institutes of Health (5r01ey012370-05)
- National Eye Institute (R01EY014102, R01 EY12370, R01EY011234, R01EY010559)
- National Cancer Institute (R01CA091645)
- 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 › Neurology › Barrier Structure and Function Studies
- Keywords
- angiopoietin-2, angiopoietin-1, Tie2 receptor, VEGF-A, angiogenesis, capillary structure, endothelial cell survival, endothelial cell death, vessel regression, endothelial cell proliferation, endothelial cell migration, capillary diameter, pupillary membrane, ocular microvasculature
- MeSH terms
- Animals, Capillaries, Cell Division, Cornea, Endothelium, Vascular, Enzyme Inhibitors, Humans, Lymphokines, Muscle, Smooth, Vascular, Proteins, Recombinant Proteins, Endothelial Growth Factors, Rats, Sprague-Dawley, Apoptosis, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Angiopoietin-2, Rats
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