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

Abstract

The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components which covers the vascular endothelium. It is considered to play 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 complicate structure makes the precise assessment of the latter challenging, and many different visualization techniques have been implemented with various results. Diabetes, one of the main disease models where disorders of the glycocalyx are involved, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress with the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endothelium, more and more evidence points towards a vital role in albumin handling and, consequently, to diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a promising therapeutic target. In this review, we present the structural and functional capacities of the endothelial glycocalyx, and the available methods for its evaluation. Then, we describe the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, the current data on the field and possible treatment options targeting the glycocalyx.