Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target.

Background: The onset of many disease processes depends on the function of the endothelial cell (EC) glycocalyx (GCX) which acts as a flow-dependent barrier to cellular infiltration and molecular transport across the blood vessel wall.

Objective: This review aims to examine these processes with the potential end goal of implementing GCX repair to restore EC barrier function and slow the progression of disease.

Methods: Cell and mouse studies were employed to examine the state of EC GCX in healthy versus disruptive flow conditions. Correlations of observations of the GCX with a number of EC functions were sought with an emphasis on studies of trans-endothelial barrier integrity against vessel wall infiltration of cells and molecules from the circulation. To demonstrate the importance of GCX as a regulator of trans-endothelial infiltration, assays were performed using ECs with an intact GCX and compared to assays of ECs with an experimentally degraded GCX. Studies were also conducted of ECs in which a degraded GCX was repaired.

Results: In healthy flow conditions, the EC GCX was found to be thick and substantially covered the endothelial surface. GCX expression dropped significantly in complex flow conditions and coincided with a disease-like cellular and molecular accumulation in the endothelium or within the blood vessel wall. Therapeutic repair of the GCX abolished this accumulation.

Conclusions: Regenerating the degraded GCX reverses EC barrier dysfunction and may attenuate the progression of vascular disease.