Functional consequences of inborn and acquired errors in endothelial glycocalyx heparan sulfates

This thesis focuses on the relevance of endothelial glycocalyx in cardiometabolic disease. The glycocalyx is a glycoprotein-polysaccharide cover that surrounds the cell membranes of nearly all cells. In part I, we describe the effects of various pro-atherogenic stimuli on the endothelial glycocalyx, as well as the potential to use the endothelial glycocalyx as a therapeutic target in the prevention of cardiovascular disease progression. We found that endothelial glycocalyx volume is reduced in patients with type 1 and type 2 diabetes and in patients with Familial Hypercholesterolemia. Furthermore, glycocalyx dimensions improved after supplementation with glycocalyx precursors and statin treatment respectively. We also show that inflammation induces glycocalyx damage, which can be attenuated by anti-inflammatory treatment. To address the function of individual components of the glycocalyx into more detail, part II of this thesis presents a series of studies focusing on the consequences of inborn and acquired changes in heparan sulfate expression in cell culture experiments, animal models and in human studies. We show that heparan sulfates are involved in signal transduction in endothelial cells and in pancreatic development in humans. Finally, we show that heparan sulfates serve as receptors for triglyceride-rich lipoproteins in humans.