Time-line of glycocalyx research by the team



Hans Vink gets intrigued by the earlier suggested presence of a relatively thick glycocalyx in capillaries by Klitzman & Duling. At that time Hans is studying capillary red blood cell velocity-flux relationships as part of his PhD research at the Academic Medical Center in Amsterdam, under supervision of Prof. Jos Spaan. His interest is further established when he gets the chance to visit the group of Prof. Brian Duling at the University of Virginia in Charlottesville for a short period.



After finishing his PhD thesis in Amsterdam, Hans moves for two years to Charlottesville where he has the opportunity to investigate the properties and dimensions of the glycocalyx using advanced microscopic techniques. There, the concept of a relatively thick, permselective endothelial glycocalyx is supported experimentally by directly visualizing the exclusion of red blood cells from the capillary endothelial glycocalyx (see movie 1 & Figure 1).


Figure 1:


Movie 1:


The studies show that the glycocalyx constitutes an important permeability barrier to which macromolecules in the circulating blood have limited access dependent on their molecular size and charge. These findings have important functional implications with regard to the regulation of perfused capillary blood volume and exchange capacity.



Upon returning to the Academic Medical Center in Amsterdam, Hans and Jos Spaan get funded by a 5 year program grant from the Netherlands Organisation for Scientific Research (NWO). New members join the glycocalyx research group and the focus of the study of the glycocalyx broadens. By carefully preserving the carbohydrate structures on the endothelium, Bernard van den Berg is able to visualize a thick glycocalyx backbone in the coronary circulation with electron microscopy; enzymatic degradation of these structures is associated with significant myocardial edema (Figure 2).


Figure 2:


Research on the functional consequences of the presence of this thick glycocalyx for coronary  blood flow and volume regulation starts when Jurgen van Teeffelen joins the glycocalyx group. Also, use of sugar degrading enzymes such as hyaluronidase reveal important roles for the glycocalyx in vascular protection: loss of glycocalyx integrity is accompanied by impaired endothelial mechanotransduction of fluid shear stress, adhesion of platelets and leukocytes to the capillary and venular endothelial surface, and leakage of plasma proteins and fluid from the vascular compartment, resulting in swelling of the pericapillary interstitial space and consequent compression of the anatomic capillary lumen (Figure 3).


Figure 3:


Also, experimental studies are initiated showing that rapid glycocalyx perturbation occurs when the circulation gets exposed to atherogenic stimuli such as oxidized lipoproteins, hyperlipidemia, and hyperglycemia. Finally, in a collaboration with the department of Vascular Medicine (Prof. Erik Stroes), studies defining the dimensions of the glycocalyx in the human body are initiated. These studies clearly show that the glycocalyx is a voluminous compartment in the human circulation with important protective functions regarding homeostasis of the vascular wall. Furthermore, these studies indicate that the glycocalyx is damaged in the presence of cardiovascular risk factors such as diabetes.



The glycocalyx team moves to the department of Physiology, Maastricht University. Increasing insight in the structure of the glycocalyx in large arteries are obtained using advanced microscopy techniques; these studies reveal that the glycocalyx is even much thicker in these larger vessels than in the microcirculation, but that its dimensions and barrier properties are greatly compromised at locations that are prone to the development of atherosclerotic lesions.


The contribution of a recruitment of the glycocalyx in the coronary blood volume increase by the vasodilator adenosine is established, while a role for the glycocalyx in regulation of insulin delivery and insulin-mediated glucose uptake in skeletal muscle is indicated. Further, new diagnostic tools are developed enabling on-line appraisal of glycocalyx damage in humans by non-invasive imaging.


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