Cited by 676Angiogenesis and VEGF in CancerLymphatic System and DiseasesBarrier Structure and Function Studies

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Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo

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Lobov, Ivan B., Brooks, Peter C., Lang, Richard A.·2002·Proceedings of the National Academy of Sciences

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Abstract

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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Authors: Lobov, I. B., Brooks, P. C., & Lang, R. A.
Affiliations: Cincinnati Children's Hospital Medical Center (US)
Corresponding author: Lang, Richard A.
ORCID: Lobov, Ivan B.
Brooks, Peter C.
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
DOI: 10.1073/pnas.172161899
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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Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo

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