ArticleJCI insight2022
Glycocalyx heparan sulfate cleavage promotes endothelial cell angiopoietin-2 expression by impairing shear stress-related AMPK/FoxO1 signaling.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
28 citing papers in PubMed, 39 citations in OpenAlex.
- Restrictive Versus Standard Intravenous Fluid Therapy and Endothelial Glycocalyx Shedding in ICU Patients With Septic Shock-A Preplanned Sub-Study of the Randomized CLASSIC Trial.Acta anaesthesiologica Scandinavica · 2026Trial
- Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients.Scientific reports · 2024Trial
- Endothelial glycocalyx perturbation in obstructive sleep apnea is associated with repetitive hypoxemia and immunothrombotic endothelial dysfunction.Journal of translational medicine · 2026Article
- The emerging role of heparanase in cardiovascular diseases: Pathophysiology, clinical outcomes, and therapeutic perspectives.Journal of thrombosis and thrombolysis · 2026Review
- Article
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Multimodal Profiling Reveals Distinct Endothelial Activation Pathways Regulated by Flow and Heparan Sulfate.Cellular and molecular bioengineering · 2026Article
- Association between serum endothelial glycocalyx biomarkers and prognosis in paediatric sepsis.BMC infectious diseases · 2026Observational
- Article
- Cell-specific exosomes in sepsis-associated ARDS: from immunometabolic reprogramming to precision medicine.Frontiers in immunology · 2026Review
- Age-related differences in circulating heparanase-1 activity in sepsis and correlation with systemic vascular endotheliopathy.Frontiers in medicine · 2026Article
- Evaluation of Endothelial Glycocalyx Damage in Neonatal Lambs With Diarrhoea: A Biomarker-Based Approach.Veterinary medicine and science · 2025Article
- Heart Failure Impacts Endothelial Cell Responses to Cardiac Surgery on Cardiopulmonary Bypass.Cells · 2025Article
- Angiopoietin-1 and Tie2-Based Dual Cell Therapy Enhances Antiangiogenic Barrier Function in a Retina-Mimetic Model for Neovascular Retinal Disease.Tissue engineering and regenerative medicine · 2025Article
- Injury induced endotheliopathy: overview, diagnosis, and management.Current opinion in critical care · 2025Review
- The glycocalyx: a key target for treatment of severe acute pancreatitis-associated multiple organ dysfunction syndrome.Human cell · 2025Review
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
- Role of the endothelial cell glycocalyx in sepsis-induced acute kidney injury.Frontiers in medicine · 2025Review
- AMP dependent protein kinase regulates endothelial heparan sulfate expression in response to an inflammatory stimulus under arterial shear stress.Biochemical and biophysical research communications · 2024Article
- Shear Stress-Induced AMP-Activated Protein Kinase Modulation in Endothelial Cells: Its Role in Metabolic Adaptions and Cardiovascular Disease.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Angiopoietin-2 (Ang-2) is a key mediator of vascular disease during sepsis, and elevated plasma levels of Ang-2 are associated with organ injury scores and poor clinical outcomes. We have previously observed that biomarkers of endothelial glycocalyx (EG) damage correlate with plasma Ang-2 levels, suggesting a potential mechanistic linkage between EG injury and Ang-2 expression during states of systemic inflammation. However, the cell signaling mechanisms regulating Ang-2 expression following EG damage are unknown. In the current study, we determined the temporal associations between plasma heparan sulfate (HS) levels as a marker of EG erosion and plasma Ang-2 levels in children with sepsis and in mouse models of sepsis. Second, we evaluated the role of shear stress-mediated 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling in Ang-2 expression following enzymatic HS cleavage from the surface of human primary lung microvascular endothelial cells (HLMVECs). We found that plasma HS levels peaked before plasma Ang-2 levels in children and mice with sepsis. Further, we discovered that impaired AMPK signaling contributed to increased Ang-2 expression following HS cleavage from flow-conditioned HLMVECs, establishing a paradigm by which Ang-2 may be upregulated during 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 Socratic graph.