The pathological relevance of increased endothelial glycocalyx permeability

The endothelial glycocalyx is a vital regulator of vascular protein permeability and hydraulic conductivity. Damage to this delicate layer can result in increased protein and water transit. The clinical importance of albuminuria as a predictor of kidney disease progression and vascular disease has driven research in this area. In this review we outline how research to date has attempted to measure the contribution of the endothelial glycocalyx to vessel wall permeability. We discuss the contrasting published results, comparing evidence for the role of the endothelial glycocalyx in regulating permeability in discrete areas of the vasculature and highlight the inherent limitations of the data that has been produced to date. In particular we draw the readers attention to the difficulties in interpreting a normal urinary albumin level in early disease models. In addition, we summarise the research supporting the view that glycocalyx damage is a key pathological step in a diverse array of clinical conditions including diabetic complications, sepsis, preeclampsia and atherosclerosis. Finally, we discuss novel methodologies including an ex vivo glomerular permeability assay that should advance our understanding of permeability changes in disease.