Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.
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.
Nieuwdorp
Max
M
Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
van Haeften
Timon W
TW
Gouverneur
Mirella C L G
MC
Mooij
Hans L
HL
van Lieshout
Miriam H P
MH
Levi
Marcel
M
Meijers
Joost C M
JC
Holleman
Frits
F
Hoekstra
Joost B L
JB
Vink
Hans
H
Kastelein
John J P
JJ
Stroes
Erik S G
ES
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
D003911:Dextrans; D008353:Mannitol; D005947:Glucose; D000111:Acetylcysteine