title: Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.
abstract: Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability. The systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects. Measurements were performed in random order on five occasions: two control measurements, two measurements during normoinsulinemic hyperglycemia with or without N-acetylcysteine (NAC) infusion, and one during mannitol infusion. Glycocalyx measurements were reproducible (1.7 +/- 0.2 vs. 1.7 +/- 0.3 l). Hyperglycemia reduced glycocalyx volume (to 0.8 +/- 0.2 l; P < 0.05), and NAC was able to prevent the reduction (1.4 +/- 0.2 l). Mannitol infusion had no effect on glycocalyx volume (1.6 +/- 0.1 l). Hyperglycemia resulted in endothelial dysfunction, increased plasma hyaluronan levels (from 70 +/- 6 to 112 +/- 16 ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 + 2: from 0.4 +/- 0.1 to 1.1 +/- 0.2 nmol/l; d-dimer: from 0.27 +/- 0.1 to 0.55 +/- 0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Nieuwdorp
authors.forename: Timon W
authors.initials: TW
authors.lastname: van Haeften
authors.forename: Mirella C L G
authors.initials: MC
authors.lastname: Gouverneur
authors.forename: Hans L
authors.initials: HL
authors.lastname: Mooij
authors.forename: Miriam H P
authors.initials: MH
authors.lastname: van Lieshout
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Frits
authors.initials: F
authors.lastname: Holleman
authors.forename: Joost B L
authors.initials: JB
authors.lastname: Hoekstra
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D001777:Blood Coagulation; D003911:Dextrans / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D013997:Time Factors
chemical_list: D003911:Dextrans; D008353:Mannitol; D005947:Glucose; D000111:Acetylcysteine