Endothelial cell dysfunction and glycocalyx – A vicious circle

Dysfunctional endothelial cells are an essential contributor to the progression of diverse chronic cardiovascular, renal, and metabolic diseases. It manifests in impairment of nitric oxide-dependent vasorelaxation, vascular permeability, and leukocytes deterrent. While endothelial glycocalyx is known to regulate these functions, glycocalyx has been shown to be impaired in pathologic settings leading to endothelial dysfunction. Are these findings coincidental or are they indicative of a potential cooperation of the glycocalyx and the endothelium in inducing a dysfunctional phenotype? The main thrust of this overview is to advance a hypothesis on the existence of vicious circle relations between impaired endothelial glycocalyx and endothelial cell dysfunction. We briefly introduce physiology and pathology of blood flow-induced components of mechanotransduction in endothelial cells, as this function is dependent on glycocalyx and is critically involved in the development of endothelial dysfunction. Next, we present a series of experimental findings and arguments favoring the view on the impairment of mechanotransduction in dysfunctional endothelia. We advance the concept of feedback reinforcement between perturbed endothelial glycocalyx and progression of endothelial dysfunction and sketch therapeutic approaches to restore them. Among those we introduce our recently designed liposomal nanocarriers of preassembled glycocalyx and present evidence of their ability to expeditiously restore endothelial mechanotransduction. •Endothelial cell dysfunction is the bedrock of diverse cardiovascular, renal, and metabolic diseases.•Degraded endothelial glycocalyx and impaired mechanotransduction are manifestations of endothelial dysfunction.•The pathways connecting endothelial dysfunction with the degradation of glycocalyx are mutually reinforced. Such a conceptual link renders therapeutic benefits.•Existing strategies to restore glycocalyx and/or ameliorate endothelial dysfunction.•Recent findings with liposomal nanocarriers of the preassembled glycocalyx, which engender a dual effect of regenerating endothelial glycocalyx and improving endothelial mechanotransduction and nitric oxide production.