ArticleAngiogenesis2017
Identification of HIF-2α-regulated genes that play a role in human microvascular endothelial sprouting during prolonged hypoxia in vitro.
Article in Angiogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood.International journal of molecular sciences · 2020Trial
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- Understanding the Impact of Hypoxia on Pulmonary Artery Endothelial Cells in Chronic Thromboembolic Pulmonary Hypertension Patients.International journal of molecular sciences · 2026Article
- KDM6B promotes VEGFA expression and vasculogenic mimicry in glioblastoma cells under hypoxia conditions.Experimental brain research · 2026Article
- Single-cell transcriptomic profiling reveals cell type heterogeneity between HFpEF and HFrEF.Communications biology · 2025Article
- Article
- Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion.International journal of molecular sciences · 2024Article
- The Oxygen Cascade from Atmosphere to Mitochondria as a Tool to Understand the (Mal)adaptation to Hypoxia.International journal of molecular sciences · 2023Review
- Effect of Hypoxia on Pulmonary Endothelial Cells from Bleomycin-Induced Pulmonary Fibrosis Model Mice.International journal of molecular sciences · 2022Article
- Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery.Current drug metabolism · 2022Article
- Article
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- Phenotypic diversity and metabolic specialization of renal endothelial cells.Nature reviews. Nephrology · 2021Review
- Mechanical forces and metabolic changes cooperate to drive cellular memory and endothelial phenotypes.Current topics in membranes · 2021Review
- Absence of HTATIP2 Expression in A549 Lung Adenocarcinoma Cells Promotes Tumor Plasticity in Response to Hypoxic Stress.Cancers · 2020Article
- Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia.PloS one · 2020Article
- Review
- Profiling the unique protective properties of intracranial arterial endothelial cells.Acta neuropathologica communications · 2019Article
- Primary endothelial cell-specific regulation of hypoxia-inducible factor (HIF)-1 and HIF-2 and their target gene expression profiles during hypoxia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Matrine has pro-apoptotic effects on liver cancer by triggering mitochondrial fission and activating Mst1-JNK signalling pathways.The journal of physiological sciences : JPS · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During prolonged hypoxic conditions, endothelial cells change their gene expression to adjust to the low oxygen environment. This process is mainly regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Although endothelial cells do not form sprouts during prolonged hypoxic culturing, silencing of HIF-2α partially restores sprout formation. The present study identifies novel HIF-2α-target genes that may regulate endothelial sprouting during prolonged hypoxia. The gene expression profile of primary human microvascular endothelial cells (hMVECs) that were cultured at 20 % oxygen was compared to hMVECs that were cultured at 1 % oxygen for 14 days by using genome-wide RNA-sequencing. The differentially regulated genes in hypoxia were compared to the genes that were differentially regulated upon silencing of HIF-2α in hypoxia. Surprisingly, KEGG pathway analysis showed that metabolic pathways were enriched within genes upregulated in response to hypoxia and enriched within genes downregulated upon HIF-2α silencing. Moreover, 51 HIF-2α-regulated genes were screened for their role in endothelial sprouting in hypoxia, of which four genes ARRDC3, MME, PPARG and RALGPS2 directly influenced endothelial sprouting during prolonged hypoxic culturing. The manipulation of specific downstream targets of HIF-2α provides a new, but to be further evaluated, perspective for restoring reduced neovascularization in several pathological conditions, such as diabetic ulcers or other chronic wounds, for improvement of vascularization of implanted tissue-engineered scaffolds.
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