Endothelial-erythrocyte glycocalyx exchange enables liquid biopsies of endothelial function

The luminal surface of blood vessels is covered by a hydrated mesh of sugars and proteins termed the endothelial glycocalyx. The glycocalyx forms a permeability barrier and helps regulate leucocyte migration. Directly detecting glycocalyx damage could provide a major advance in vascular health monitoring. Here we show that red blood cell glycocalyx mirrors the endothelial glycocalyx in health and disease. Using peripherally sampled blood, we confirm that red blood cell glycocalyx measurements predict cardiac and renal endothelial glycocalyx alterations and direct measures of endothelial barrier function in male rats. To investigate the underlying mechanism, we use Azide-Alkyne cycloaddition (‘Click’ chemistry) to confirm that contact between endothelial and red blood cells results in continual reciprocal transfer of glycocalyx components. These discoveries facilitate real-time monitoring of endothelial damage in patients whilst simultaneously providing a potential explanation as to how red blood cells maintain their glycocalyx during circulation.