The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Hypoxia-Inducible Factor-1 Mediates Activation of Cultured Vascular Endothelial Cells by Inducing Multiple Angiogenic Factors
Open accessAbstract
Hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of vascular endothelial growth factor (VEGF) and other hypoxia-responsive genes. Transgenic expression of a constitutively stable HIF-1alpha mutant increases the number of vascular vessels without vascular leakage, tissue edema, or inflammation. This study aimed to investigate the molecular basis by which HIF-1 mediates the angiogenic response to hypoxia. In primary human endothelial cells, hypoxia, desferrioxamine, or infection with Ad2/HIF-1alpha/VP16, an adenoviral vector encoding a constitutively stable hybrid form of HIF-1alpha, increased the mRNA and protein levels of VEGF, angiopoietin-2 (Ang-2), and angiopoietin-4 (Ang-4). Infection with Ad2/CMVEV (a control vector expressing no transgene) had no effect. Angiopoietin-1 (Ang-1) expression was not detected in human endothelial cells. Ang-4 was also induced by hypoxia or Ad2/HIF-1alpha/VP16 in human cardiac cells, whereas Ang-1 expression remained unchanged. Recombinant Ang-4 protein protected endothelial cells against serum starvation-induced apoptosis and increased cultured endothelial cell migration and tube formation. Ad2/HIF-1alpha/VP16 stimulated endothelial cell proliferation and tube formation. Hypoxia- or Ad2/HIF-1alpha/VP16-induced tube formation was significantly reduced by a Tie-2 inhibitor. These results suggest that HIF-1 mediates the angiogenic response to hypoxia by upregulating the expression of multiple angiogenic factors. Ang-4 can function similarly as Ang-1 and substitute for Ang-1 to participate in hypoxia-induced angiogenesis. Activation of the angiopoietin/Tie-2 system may play a role in the ability of HIF-1 to induce hypervascularity without excessive permeability.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The activation of HIF-1α and the formation of the HIF complex induce several angiogenic growth factor genes, including VEGF and stromal cell-derived factor-1 (SDF-1)/C-X-C motif chemokine 12 (CXCL12) [82,83,84].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [84]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Risau, W. (1997) · Nature · doi:10.1038/386671a0 · Cited by 5,727
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., et al. (1997) · Science · doi:10.1126/science.277.5322.55 · Cited by 3,570
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis
Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S. H., Sato, T. N., & Yancopoulos, G. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81813-9 · Cited by 2,872
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF
Holash, J. A., Maisonpierre, P. C., Compton, D. L., Boland, P., Alexander, C., Zagzag, D., Yancopoulos, G. D., & Wiegand, S. J. (1999) · Science · doi:10.1126/science.284.5422.1994 · Cited by 2,222
Purification and Characterization of Hypoxia-inducible Factor 1
Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094
Cited by
Sorted by citations
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154
Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M. C., & Martelli, F. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800731200 · Cited by 912
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Kaur, B., Khwaja, F. W., Severson, E. A., Matheny, S. L., Brat, D. J., & Van Meir, E. G. (2005) · Neuro-Oncology · doi:10.1215/s1152851704001115 · Cited by 725
Therapeutic targeting of the angiopoietin–TIE pathway
Saharinen, P., Eklund, L., & Alitalo, K. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.278 · Cited by 620
Metadata
- Authors
- Yamakawa, M., Liu, L. X., Date, T., Belanger, A. J., Vincent, K. A., Akita, G. Y., Kuriyama, T., Cheng, S. H., Gregory, R. J., & Jiang, C.
- Affiliations
- Chiba University (JP)
- Venue
- Circulation Research
- Published
- 2003-10-03
- Volume
- 93
- Issue
- 7
- Pages
- 664-673
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2171354819
- Cited by
- 327
- References
- 48
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 12 · 2017: 13 · 2016: 21 · 2015: 15 · 2014: 12 · 2013: 17 · 2012: 15
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- HIF-1, HIF-1α, angiogenesis, hypoxia, vascular endothelial cells, vascular endothelial growth factor, angiopoietin-2, angiopoietin-4, angiopoietin-1, Tie2, endothelial cell migration, tube formation, endothelial cell proliferation, apoptosis, deferoxamine, hypervascularity, vascular permeability
- MeSH terms
- Placenta Growth Factor, Blood Vessels, Cell Division, Cell Membrane Permeability, Cell Movement, Cells, Cultured, Deferoxamine, DNA-Binding Proteins, Endothelium, Vascular, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Genetic Vectors, Humans, Lymphokines, Nuclear Proteins, Platelet-Derived Growth Factor, Pregnancy Proteins, RNA, Messenger, Transcription Factors, Cell Hypoxia, Endothelial Growth Factors, Apoptosis, Caspases, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Angiopoietins, Angiopoietin-2, Receptor, TIE-2, Angiogenesis Inducing Agents, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Caspase 3
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
