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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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“In addition, the Ang-2/Tie2 cascade regulated the early steps of angiogenesis associated with one of more angiogenic factors, the VEGF-A/VEGF-R2 cascade (Lobov et al., 2002; Scholz et al., 2015).”
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CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization
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“More specifically, Ang2 has been shown to incite endothelial cell death and regression in low VEGF-A environments and may act cooperatively with declining VEGF-A levels to signal glomeruloid body involution (45).”
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Quantum Dot Self-Assembly for Protein Detection with Sub-Picomolar Sensitivity
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BackgroundOcular versus Extraocular Neovascularization: Mirror Images or Vague Resemblances
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“Ang-2 may stimulate microvessel sprouting and angiogenesis in the presence of VEGF (Zhu et al., 2005; Lobov et al., 2002).”
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“Thus, the Ang/Tie2 system seems to play an important role in vascular network remodeling [26] and in the pathogenesis and progression of NETs [27].”
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“Ang-2 Angiopoietin-2 Promotes vessel sprouting with VEGF; exerts vascular destabilizing effects [62,63]”
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“Basically, when capillary sprouting is induced by factors besides VEGF165, Ang-2 may contribute to the arrest of angiogenesis rather than support it [39].”
BackgroundControl of the blood–brain barrier function in cancer cell metastasis
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“VEGF acts in concert with angiopoietin-2 to regulate vessel growth (Lobov et al., 2002; Saharinen et al., 2011).”
BackgroundInfluentialIntegrins as “functional hubs” in the regulation of pathological angiogenesis
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“, pericytes [14]), endothelial cell death, and vessel regression [38].”
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“Conversely, pro-inflammatory cytokines TNF-α, IL-1β and vascular permeability factor, VEGF, mediate the release of angiopoietin-2, an antagonist to angiopoietin-1 [48,107], that promotes increased vascular inflammation [108], disruption of angiogenesis [109], endothelial cell death [110] and vascular regression [110,1…”
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“Various VEGF-A isoforms are present in the developing lung.”
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“, 1996), whereas angiopoietin 2 acts as an antagonist by binding to the Tie-2 receptor without transmitting a signal (Maisonpierre et al., 1997; Lobov et al., 2002).”
BackgroundAutocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease
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“Overexpression of angiopoietin-2 has been implicated in the activation of signals leading to a disassembly of the junctional complex under physiological proangiogenic conditions and in a number of cerebrovascular disorders.(8) We hypothesized, first, that circulating MMD serum constituents promote an elevation of angi…”
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“In addition, VEGFA is important for the normal differentiation of progenitor cells into hypertrophic chondrocytes, osteoblasts and osteoclasts (Maes et al., 2002, 2004).”
BackgroundUnderstanding endothelial cell apoptosis: what can the transcriptome, glycome and proteome reveal?
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“Vascular endothelial (VE) cadherin is an EC–EC adhesion molecule that transduces anti-apoptoic signals into EC in conjunction with VEGF-A.”
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“high and low levels of VEGF, respectively (23, 24).”
Anti-VEGF antibody enhances the antitumor effect of CD40
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“In the presence of endogenous VEGF-A, Ang-2 increases tumor angiogenesis by promoting vessel destabilization, whereas Ang-2 promotes endothelial cell death and vessel regression in the absence of VEGF-A [34].”
BackgroundDifferential levels of soluble angiopoietin‐2 and Tie‐2 in patients with haematological malignancies
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“vascular regression and apoptosis, depending on the presence of VEGF (15).”
BackgroundInfluentialTian, Y., Huang, Z., Wang, Z., Yin, C., Zhou, L., Zhang, L., Huang, K., Zhou, H., Jiang, X., Li, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084150 · Cited by 40
“The angiogenesis family member Ang2 was initially regarded as vascular remodeling antagonist of Ang1 [32,33], later on, the concerted action of Ang2 and VEGF-A was noticed on endothelial cells [34,35].”
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LRP5 Regulates Development of Lung Microvessels and Alveoli through the Angiopoietin-Tie2 Pathway
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“Also, Ang-2 promotes or inhibits angiogenesis in different micro-environments (Thurston et al. 2000; Jones et al. 2001; Lobov et al. 2002; Zhu et al. 2005).”
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“This results in the absence of VEGF in vessel regression, whereas in concert with VEGF Ang2 induces endothelial cell migration and proliferation [19].”
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“Ang-2 is expressed predominantly at sites of vascular remodeling and can cause vascular disruption [6,9,10].”
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“Pericytes in the hyaloid vessels express Ang2, which promotes endothelial cell death and capillary regression (Lobov et al., 2002; Rao et al., 2007; Yancopoulos et al., 2000).”
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“Mechanistic research in tumor angiogenesis indicates that the Ang/Tie system works together with the VEGF system to break down and remodel tumor blood vessels (25).”
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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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