ArticleThe EMBO journal2022
Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review.Aging and disease · 2024Pooled it
- Cell Therapy as Metabolic Rescue after Ischemic Stroke: Rewiring Bioenergetics, Redox Homeostasis, and Neurovascular Repair.Stem cell reviews and reports · 2026Review
- Effects of liraglutide on gut bacterial community dynamics.Microbiology spectrum · 2026Article
- Review
- Peri-Microvascular Glycogen and Lactate Regulate Capillary Constrictions and Ischemia Outcome in Mice.Journal of neurochemistry · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2026Article
- The lactate shuttle in ageing: a metabolic bridge between muscle fatigue and brain resilience.Frontiers in physiology · 2026Review
- Effects of maternal autoantibody exposure at the cellular level: implications for the developing brain.Frontiers in psychiatry · 2026Review
- Integrated Mendelian Randomization and Single-Cell RNA Sequencing Analyses Reveal Lactate Metabolism as a Key Pathway in COVID-19-Induced Pulmonary Fibrosis.Canadian respiratory journal · 2026Article
- The Endothelium as a Central Mediator of Exercise-Induced Metabolism and Communication.Exercise and sport sciences reviews · 2026Review
- Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders.Frontiers in molecular neuroscience · 2026Review
- Machine learning-enabled spatial multi-omics uncovers lactate-driven targets and tumor microenvironmental reprogramming in cancer.NPJ digital medicine · 2025Article
- The canine blood-brain barrier in health and disease: focus on brain protection.The veterinary quarterly · 2025Review
- Tumor exosomal miR-221-3p induces glycolysis through the LIFR/GLUT1 pathway to destroy the cerebral vascular endothelial cell barrier and promote breast cancer brain metastasis.Journal of translational medicine · 2025Article
- Salt-sensitive hypertension promotes neuronal mitochondrial stress and neurodegenerative alterations via neuro-vascular metabolic reprogramming and local RAS signaling.Journal of neuroinflammation · 2025Article
- Brain Endothelial Cells in Blood-Brain Barrier Regulation and Neurological Therapy.International journal of molecular sciences · 2025Review
- Exploring Endothelial Cell Dysfunction's Impact on the Brain-Retina Microenvironment Connection: Molecular Mechanisms and Implications.Molecular neurobiology · 2025Review
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
Abstract
Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood-brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood-brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.
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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.