Cited by 460Angiogenesis and VEGF in CancerDevelopmental Biology and Gene RegulationBarrier Structure and Function Studies

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The transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling

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Peng, Jun, Zhang, Liyong, Drysdale, Linsay, Fong, Guo-Hua·2000·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.140087397PMC PMC26957

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Abstract

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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BackgroundInfluential
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Background
HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta
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“Epas1/EPAS1 (HIF-2α) Embryonic lethal with bradycardia due to defective catecholamine homeostasis [33], vascular remodelling defects [34], cardiac failure and neonatal lethal with respiratory failure [35].”
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Authors: Peng, J., Zhang, L., Drysdale, L., & Fong, G.-H.
Affiliations: Western University (CA)
ORCID: Peng, Jun
Zhang, Liyong
Fong, Guo-Hua
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
DOI: 10.1073/pnas.140087397
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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The transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling

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