Loss of Endothelial Glycocalyx During Acute Hyperglycemia Coincides With Endothelial Dysfunction and Coagulation Activation In Vivo

  1. Max Nieuwdorp1,
  2. Timon W. van Haeften2,
  3. Mirella C.L.G. Gouverneur3,
  4. Hans L. Mooij1,
  5. Miriam H.P. van Lieshout1,
  6. Marcel Levi4,
  7. Joost C.M. Meijers1,
  8. Frits Holleman4,
  9. Joost B.L. Hoekstra4,
  10. Hans Vink3,
  11. John J.P. Kastelein1 and
  12. Erik S.G. Stroes1
  1. 1Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
  2. 2Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
  3. 3Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands
  4. 4Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands
  1. Address correspondence and reprint requests to Erik S.G. Stroes, MD, PhD, Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Rm. F4-159.2, 1105 AZ, Amsterdam, Netherlands. E-mail: e.s.stroes{at}amc.uva.nl


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.


    • Accepted October 25, 2005.
    • Received August 24, 2005.
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