ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 262 citations in OpenAlex.
- The effects of balanced crystalloid versus plasma on endothelial injury, systemic inflammation, and coagulation in experimental endotoxaemia: a randomised human volunteer study.British journal of anaesthesia · 2026Trial
- Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2024Trial
- Effect of goal-directed fluid therapy based on plasma colloid osmotic pressure on the postoperative pulmonary complications of older patients undergoing major abdominal surgery.World journal of surgical oncology · 2023Trial
- Trial
- Graft glycocalyx degradation in human liver transplantation.PloS one · 2019Trial
- Article
- Advancing Microcirculatory Therapies in Pediatric Sepsis: Current Opportunities and Future Directions.Journal of intensive care medicine · 2026Review
- Evaluating the endothelial glycocalyx from bench to bedside: a translational framework for microvascular assessment.Angiogenesis · 2026Review
- Glycation at the Gate: A Brain Endothelial Glycocalyx Model and Therapeutic Roadmap for Alzheimer's Disease.Biomedicines · 2026Article
- Sepsis-induced endothelial glycocalyx disruption and remodeling: an ultrastructural study in mice.Intensive care medicine experimental · 2026Article
- Exercise-Induced Shear Stress, Endothelial Glycocalyx Remodeling, and Atherosclerotic Plaque Stability: A Mechanistic Review.Journal of cardiovascular development and disease · 2026Review
- Beyond blood pressure: a comprehensive overview of clinical indices in shock and tissue hypoperfusion.Acute and critical care · 2026Article
- The Role of Endothelial Glycocalyx in the Pathophysiology of Chronic Kidney Disease and Hypertension: From Molecular Mechanisms to Clinical Biomarkers.Life (Basel, Switzerland) · 2026Review
- Endothelial glycocalyx degradation and its association with clinical outcomes and host response aberrations in community-acquired pneumonia across different care settings.Critical care (London, England) · 2026Article
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- The Molecular Structure of the Endothelial Glycocalyx. Models to Interpret High-Resolution Imaging of an Ordered Structure for the Molecular Filter at the Microvascular Wall.Advances in experimental medicine and biology · 2026Article
- Molecular Crosstalk Between Intrauterine hCG and Endometrial Receptivity: Signalling Pathways, Immune Modulation, and Translational Perspectives in IVF.International journal of molecular sciences · 2025Review
- The Endothelial Glycocalyx: The First Line of Defense in the Prevention and Treatment of Kidney Diseases.Kidney medicine · 2025Review
- Association Between Serum Syndecan 1 Levels and Metabolic Syndrome Parameters: A Comparative Cross-Sectional Study.Endocrinology, diabetes & metabolism · 2025Article
- Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial cells (ECs) are covered by a surface glycocalyx layer that forms part of the barrier and mechanosensing functions of the blood-tissue interface. Removal of albumin in bathing media induces collapse or shedding of the glycocalyx. The electrostatic interaction between arginine residues on albumin, and negatively charged glycosaminoglycans (GAGs) in the glycocalyx have been hypothesized to stabilize the glycocalyx structure. Because albumin is one of the primary carriers of the phospholipid sphingosine-1-phosphate (S1P), we evaluated the alternate hypothesis that S1P, acting via S1P1 receptors, plays the primary role in stabilizing the endothelial glycocalyx. Using confocal microscopy on rat fat-pad ECs, we demonstrated that heparan sulfate (HS), chondroitin sulfate (CS), and ectodomain of syndecan-1 were shed from the endothelial cell surface after removal of plasma protein but were retained in the presence of S1P at concentrations of >100 nM. S1P1 receptor antagonism abolished the protection of the glycocalyx by S1P and plasma proteins. S1P reduced GAGs released after removal of plasma protein. The mechanism of protection from loss of glycocalyx components by S1P-dependent pathways was shown to be suppression of metalloproteinase (MMP) activity. General inhibition of MMPs protected against loss of CS and syndecan-1. Specific inhibition of MMP-9 and MMP-13 protected against CS loss. We conclude that S1P plays a critical role in protecting the glycocalyx via S1P1 and inhibits the protease activity-dependent shedding of CS, HS, and the syndecan-1 ectodomain. Our results provide new insight into the role for S1P in protecting the glycocalyx and maintaining vascular homeostasis.
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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.