ArticleThe EMBO journal2017
Role of glutamine and interlinked asparagine metabolism in vessel formation.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 1 of them a synthesis that pooled it.
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Who cites it
201 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.
- A systematic review of omics discovery studies to identify pertinent metabolic pathways for locally advanced rectal cancer in response to neoadjuvant chemoradiotherapy.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Endothelial SLC25A13 links glutamine metabolism to angiogenesis.EMBO molecular medicine · 2026Article
- Endothelial Dysfunction and Metabolic Reprogramming in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Excess glutamine rewires endothelial cell metabolism.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- NDUFA4L2 rescues hyperoxia-induced migration defects in retinal endothelial cells by reversing isocitrate dehydrogenase flux blockade.bioRxiv : the preprint server for biology · 2026Article
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- Amino acids: Missing link in preeclampsia pathogenesis?European journal of nutrition · 2026Observational
- Discovery of the protective effect of glutamine on acute alcoholic liver injury.Indian journal of pharmacology · 2026Article
- Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability.Journal of cardiovascular translational research · 2026Review
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- Multi-omics analysis reveals metabolic diversity underlying endothelial cell functions.Life science alliance · 2026Article
- Expression, regulation, and multifaceted molecular and biological functions of sirtuin 6 in the porcine endometrium during early pregnancy.Cell communication and signaling : CCS · 2026Article
- The glutaminase activity of ASNS fuels glutamine metabolism in leukemia.Haematologica · 2026Article
- The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells.The EMBO journal · 2026Article
- Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Müller cell glutamine metabolism links photoreceptor and endothelial injury in diabetic retinopathy.Life science alliance · 2026Article
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- The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.Cells · 2026Article
- Endothelial mitochondrial homeostasis in the development and progression of atherosclerosis.Frontiers in cardiovascular medicine · 2026Review
141 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
Abstract
Endothelial cell (EC) metabolism is emerging as a regulator of angiogenesis, but the precise role of glutamine metabolism in ECs is unknown. Here, we show that depriving ECs of glutamine or inhibiting glutaminase 1 (GLS1) caused vessel sprouting defects due to impaired proliferation and migration, and reduced pathological ocular angiogenesis. Inhibition of glutamine metabolism in ECs did not cause energy distress, but impaired tricarboxylic acid (TCA) cycle anaplerosis, macromolecule production, and redox homeostasis. Only the combination of TCA cycle replenishment plus asparagine supplementation restored the metabolic aberrations and proliferation defect caused by glutamine deprivation. Mechanistically, glutamine provided nitrogen for asparagine synthesis to sustain cellular homeostasis. While ECs can take up asparagine, silencing asparagine synthetase (ASNS, which converts glutamine-derived nitrogen and aspartate to asparagine) impaired EC sprouting even in the presence of glutamine and asparagine. Asparagine further proved crucial in glutamine-deprived ECs to restore protein synthesis, suppress ER stress, and reactivate mTOR signaling. These findings reveal a novel link between endothelial glutamine and asparagine metabolism in vessel sprouting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.