The Endothelial Glycocalyx as a Key Mediator of Albumin Handling and the Development of Diabetic Nephropathy

The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components, which cover the vascular endothelium. It plays an important role in many physiological processes including vascular permeability, transduction of shear stress and interaction of blood cells and other molecules with the vascular wall. Its complex structure makes its precise assessment challenging, and many different visualization techniques have been used with varying results. Diabetes, one of the main disease models where disorders of the glycocalyx are present, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress due to the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endothelium, more evidence points towards a vital role in albumin handling and, consequently, in diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a promising therapeutic target. In this review, we consider the structural and functional capacities of the endothelial glycocalyx, the available methods for its evaluation, the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, and possible treatment options targeting the glycocalyx.