ArticleScience advances2022
Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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The trial behind it
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Who cites it
106 citing papers in PubMed, 150 citations in OpenAlex.
- Effects of Xuebijing combined with levosimendan on immune function and coagulation function in sepsis patients with myocardial injury.Journal of thrombosis and thrombolysis · 2026Trial
- Explainable machine learning using urinary metabolomics to predict pediatric sepsis-associated acute kidney injury: a two-center prospective observational study.Renal failure · 2026Observational
- Continuous renal replacement therapy attenuates endothelial injury biomarkers in pediatric sepsis: a prospective cohort study.Renal failure · 2026Observational
- Imeglimin pretreatment improves survival and attenuates sepsis-associated acute kidney injury following Escherichia coli challenge in diabetic mice.Clinical and experimental nephrology · 2026Article
- Salidroside alleviates sepsis-associated acute lung injury through modulation of the ERK/FoxO3a signaling axis and improvement of impaired autophagic flux.Molecular biology reports · 2026Article
- Intracellular LRG1 recruits MARCH2 to ubiquitinate and degrade endothelial VE-cadherin in septic lung injury.Acta pharmacologica Sinica · 2026Article
- MMP8 exacerbates sepsis-induced pulmonary vascular leakage by disruption of endothelial VE-cadherin through ERK signalling.Molecular biomedicine · 2026Article
- Non-canonical and constitutive activation of small GTPases: more than an exception to the rule?The Biochemical journal · 2026Review
- Nonlinear correlation between lactate levels and 28-day all-cause mortality in patients with sepsis complicated by acute respiratory distress syndrome (ARDS): a retrospective study based on the MIMIC-IV database.BMC medical informatics and decision making · 2026Article
- PRMT5/Sohlh2/Sirt1 Signaling Pathway in Vascular Endothelial Cells Modulates Lung Metastasis of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation in cardiac repair: Nexus and therapeutic opportunity.Journal of molecular and cellular cardiology plus · 2026Review
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- Targeting the GPX4-FUNDC1 Interaction with Magnesium Lithospermate B Attenuates Sepsis-Associated Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- Lactate Promotes Endothelial-Mesenchymal Transition via Mediating Twist1 Lactylation in Hypoxic Pulmonary Hypertension.International journal of molecular sciences · 2026Article
- Blocking glutamine transport normalizes lymphatic vessels in hypoxic environments by attenuating glycolysis.bioRxiv : the preprint server for biology · 2026Article
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- FGF 13 functions as a regulator of the ERK/aerobic glycolysis axis in the inflammatory state during septic lung injury.Nature communications · 2026Article
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.
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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.