(337g) Invited Speaker: Engineering Glycocalyx to Promote Atheroprotective Endothelium Function

Atherosclerosis occurs at vessel sites exposed to complex flow patterns, which damage endothelium. Proper endothelium function relies on the protective glycocalyx (GCX), which is shed in disease. Replacing it may heal ECs and slow disease progression. We studied cultured ECs and performed mice experiments, to examine endothelium in healthy and disruptive flow conditions. Immunocytochemical studies verified spatial variations in EC GCX composition. We correlated GCX composition to EC functions including vasoregulation, communication, barrier function, and vessel wall remodeling, by immunofluorescence microscopy, dye transfer and nanoparticle permeability experiments, and histology. To identify the role played by specific GCX components in EC function, some assays were performed on ECs with intact GCX and others were performed on ECs with experimentally degraded GCX. We also replaced degraded GCX components and assessed subsequent restoration of EC functions. Results demonstrated that the sialic acid (SA) component of cultured EC GCX in healthy flow is 2.66 mm thick and covers ~60% of the endothelial surface. SA thickness decreases in complex flow conditions by a significant 15%. In complex flow conditions, there is significant 58% drop in SA coverage. Heparan sulfate (HS) and hyaluronic acid GCX components were modulated differently in correlation to flow conditions. Vasoregulation, communication, barrier function, and blood vessel wall remodeling were all found to correlate to GCX composition. GCX repair by treating the cells with exogenous HS (and a co-factor) restored barrier function and recovered communication, suggesting that targeting the GCX may be a promising approach to reversing EC dysfunction and vascular disease progression.