L66	The endothelial cell glycocalyx in diabetes.
1M.Nieuwdorp, 1J.Kroon, 1H.Mooij, 2B.Atasever, 2C.Ince, 3J.Hoekstra, 1J.Kastelein, 4J.Spaan, 1E.Stroes, 4H.Vink
1Dept. Vascular Medicine, Cardiovascular Research Institute Amsterdam, AMC/UVA, Amsterdam, NL; 2Dept. Physiology, Cardiovascular Research Institute Amsterdam, AMC/UVA, Amsterdam, NL; 3Dept. Internal Medicine, Cardiovascular Research Institute Amsterdam, AMC/UVA, Amsterdam, NL; 4Dept. Medical Physics, Cardiovascular Research Institute Amsterdam, AMC/UVA, Amsterdam, NL.

Diabetes mellitus is characterized by vascular dysfunction, the exact nature of which has not been fully elucidated. Recent studies have revealed that the endothelial glycocalyx is essential for proper vascular homeostasis, preserving the vascular permeability barrier and preventing adhesion of leukocytes and platelets to the endothelium. To test the hypothesis that hyperglycemic perturbation of the glycocalyx contributes to vascular dysfunction in diabetes, we determined endothelial glycocalyx dimensions by two independent measurements (systemic as well as microvascular) in DM1 patients and matched controls. We show that systemic glycocalyx volume of healthy humans is impressively large and that glycocalyx volume is dramatically reduced to less than 30% in DM1 (from 2.4 ± 1.5 to 0.7 ± 0.9 liters, P < 0.05). This finding was substantiated by direct visualization of glycocalyx at the microvascular level, revealing that the capillary endothelial glycocalyx thickness is diminished from 0.9 ± 0.1 to 0.2 ± 0.1 µm (P < 0.05). Glycocalyx perturbation was accompanied by a 2-fold increase in systemic vascular permeability in DM1 as well as increased plasma hyaluronan levels (from 69 ± 10 to 90 ± 13 ng/ml, P < 0.05). In conclusion, our findings demonstrate that the endothelial glycocalyx is severely perturbed in DM1, which may offer a novel mechanism contributing to enhanced vascular vulnerability in diabetes. We gratefully acknowledge support from the Netherlands Organization for Scientific Research (NWO grant # 902-16-192), the Royal Netherlands Academy of Arts and Sciences (Research Fellowship to H. Vink) and the Netherlands Heart Foundation (Established Investigatorship to J. Kastelein grant # 2000D039).

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