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Sulfated glycosaminoglycans restore glycocalyx barrier properties of cultured endothelial cells in hyperglycemia
Author(s) -
Gouverneur Mirella,
Broekhuizen Lysette,
Meuwese Marijn,
Mooij Hans,
Stroes Erik,
Vink Hans
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.83
Subject(s) - glycocalyx , glycosaminoglycan , umbilical vein , vascular permeability , albumin , chemistry , barrier function , endothelium , permeability (electromagnetism) , biochemistry , medicine , in vitro , microbiology and biotechnology , biology , membrane
Background: Microalbuminuria is a clinical parameter of vascular dysfunction in patients with diabetes. The endothelial glycocalyx plays a role in regulation of vascular permeability. Therapeutic interventions using a mixture of glycosaminoglycans (GAGs) containing 80% heparin and 20% dermatan sulfate have been shown to improve vascular barrier function by reducing microalbuminuria Hypothesis: Exogenous GAGs attenuate hyperglycemia‐induced increases in endothelial permeability for albumin by restoring barrier properties of the endothelial glycocalyx. Materials and methods: Human umbilical vein endothelial cells (HUVECs) were cultured on semi‐permeable inserts and exposed to normo‐ (5mM) or hyperglycemia (25mM) for 4 days, last 24h in presence of the GAG mixture. Endothelial permeability was assessed by determining FITC‐labeled albumin transfer over the monolayer (3 hours). Additionally, the glycocalyx glucosamine sugar residues on the endothelial cells were visualized with LEA‐lectin staining Results: Albumin permeability of endothelial cells under hyperglycemia was increased to 122 ±8% (p<0.01) compared to normoglycemia. GAG incubation restored permeability in hyperglycemia (122 ±8% vs 85 ±6%; p<0.05). Additionally, LEA‐lectin revealed a 21% decrease in glucosamine staining in hyperglycemic cells which was restored following GAG mix incubation Conclusion: GAG supplementation reverses the increased trans‐endothelial albumin leakage under hyperglycemic conditions by restoring the barrier properties of the endothelial glycocalyx layer in vitro