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The transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling
Open accessAbstract
We have studied the role of the basic helix–loop–helix–PAS transcription factor EPAS-1/hypoxia-inducible factor 2α in vascular development by gene targeting. In ICR/129 Sv outbred background, more than half of the mutants displayed varying degrees of vascular disorganization, typically in the yolk sac, and died in utero between embryonic day (E)9.5 and E13.5. In mutant embryos directly derived from EPAS-1 −/− embryonic stem cells (hence in 129 Sv background), all embryos developed severe vascular defects both in the yolk sac and embryo proper and died between E9.5 and E12.5. Normal blood vessels were formed by vasculogenesis but they either fused improperly or failed to assemble into larger vessels later during development. Our results suggest that EPAS-1 plays an important role at postvasculogenesis stages and is required for the remodeling of the primary vascular network into a mature hierarchy pattern.
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“Vascularization is severely impaired in HIF1A -/- (Carmeliet et al., 1998;Ryan et al., 1998) and HIF2A -/- (Peng et al., 2000) mice.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Peng et al., 2000
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Cited by
Sorted by citations
Hypoxia — a key regulatory factor in tumour growth
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Hypoxia-inducible factors in physiology and medicine
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“5 with vascular defects (Peng et al., 2000) or bradycardia due to deficient catecholamine production (Tian et al.”
BackgroundInfluentialRegulation of angiogenesis by hypoxia: role of the HIF system
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Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
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Metadata
- Authors
- Peng, J., Zhang, L., Drysdale, L., & Fong, G.-H.
- Affiliations
- Western University (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-07-04
- Volume
- 97
- Issue
- 15
- Pages
- 8386-8391
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC26957
- OpenAlex
- W2124053736
- Cited by
- 460
- References
- 0
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 13 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 14 · 2018: 7 · 2017: 9 · 2016: 9 · 2015: 22 · 2014: 19 · 2013: 19 · 2012: 19
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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 › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- HIF-2α, vascular remodeling, vascular development, vasculogenesis, yolk sac vasculature, embryonic lethality, gene targeting, transcription factors
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Animals, Cell Line, Female, Hemorrhage, Male, Mice, Inbred ICR, Trans-Activators, Helix-Loop-Helix Motifs, Mice, Knockout, Neovascularization, Physiologic, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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