Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects

The glycocalyx is a jelly layer covering the endothelium constituted by glycosaminoglycans (GAGs), proteoglycans and adsorbed plasma proteins. This structure take part in several physiological and pathological vascular events. The glycocalyx acts as mechanosensor to shear stress and participates to regulation of vascular tone, permeability, coagulation and complement activation. Moreover it regulates the interaction and activation of blood cells with endothelial cells. The presence of a thick, normal glycocalyx is required for physiological vascular functions, whereas these functions are impaired by its damage by noxious agents. Indeed, glycocalyx alterations are involved in the pathogenesis of atherosclerosis, ischemia-reperfusion and diabetic vascular complications. GAGs such as sulodexide are promising agents to control endothelial dysfunction. They act at multiple levels: they promote glycocalyx reconstitution, control glycocalyx degrading enzymes, exert anti-inflammatory effects and have anti-apoptotic and anti-senescence effects on endothelial cells. Clinical studies support the evidence that glycosaminoglycans are useful to restore a normal endothelial function.