ArticleNature cell biology2021
Control of endothelial quiescence by FOXO-regulated metabolites.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 135 citations in OpenAlex.
- Female-specific reliance on endothelial FoxO1 governs vascular resilience and metabolic adaptation to obesity.Angiogenesis · 2026Article
- PDE4D-CXCL13 axis in gland epithelial cells promotes B cell infiltration in primary Sjögren's syndrome.Acta pharmacologica Sinica · 2026Article
- Follicle-stimulating hormone promotes energy metabolism in bovine granulosa cells through the FOXO1-ISG15 pathway to maintain the development of multiple follicles.Journal of animal science and biotechnology · 2026Article
- Salvianolic Acid A Relieves Acute Lung Injury by Promoting the Expression of FOXO1 and Activating Autophagy Through the Inhibition of miR-217-5p.Biochemical genetics · 2026Article
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- A Perturb-seq screen guided by species divergence uncovers pathways for collateral artery formation.bioRxiv : the preprint server for biology · 2026Article
- Review
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- S100B induces angiogenesis via the clathrin/FOXO1/β-catenin signaling pathway and contributes to Bevacizumab resistance in epithelial ovarian cancer.Journal of advanced research · 2026Article
- Multi-omics analysis reveals metabolic diversity underlying endothelial cell functions.Life science alliance · 2026Article
- Integrating Bidirectional Mendelian Randomization with Multi-Omics Reveals Causal Serum Metabolites and Novel Metabolic Drivers of Multiple Myeloma.International journal of molecular sciences · 2026Article
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- A Transcriptional Atlas of Endothelial Cell Zonation Along the Pulmonary Vascular Tree.bioRxiv : the preprint server for biology · 2026Article
- Decrypting spatiotemporal code of human endometrial receptivity.Nature communications · 2025Article
- Transsulfuration metabolism is essential for ferroptosis resistance in quiescent endothelial cells.Cell death & disease · 2025Article
- Targeting long-chain acylcarnitine accumulation to protect cardiac mitochondrial homeostasis after complete revascularization.Cell reports. Medicine · 2025Article
- FMO2 Promotes Angiogenesis via Regulation of N-Acetylornithine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 8 institutions in 7 countries.
Funding
Abstract
Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates S-2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits S-2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.
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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.