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Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo
Open accessAbstract
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 (89)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [89]
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“117,119 The neovascular network provides necessary nutrients and oxygen supply to cancer tissues, which is one of the key factors for tumor growth and spread.”
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“Conversely, angiopietin-1 has been found to induce maturation and to inhibit leakiness of the endothelium by reducing its responsiveness to angiogenic factors [ 12, 13 ] .”
BackgroundANG2/VEGF in steroid-refractory GVHD
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“By acting on pericytes, ANGPT2/Tie-2 destabilizes blood vessels which results in EC stimulation and secretion of angiogenic cytokines, including VEGF [22, 23, 37].”
BackgroundDevelopment and pathology of the germinal matrix
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“Conversely, in the absence of VEGF endothelial cells have been shown to undergo apoptosis, resulting in the regression of blood vessels (14).”
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Metadata
- 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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