The surface of vascular endothelial cells (ECs) is covered by a protective negatively charged layer known as the endothelial glycocalyx. Herein, we hypothesized its transport barrier and mechanosensory role in transmural water flux and low-density lipoprotein (LDL) transport in an isolated rat abdominal aorta perfused under 85 mmHg and 20 dyn/cm2 ex vivo. The endothelial glycocalyx was digested by hyaluronidase (HAase) from bovine tests. Water infiltration velocity (Vw) was measured by a graduated pipette. LDL coverage and mean maximum infiltration distance (MMID) in the vessel wall were quantified by confocal laser scanning microscopy. EC apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and leaky junction rates were evaluated by electron microscopy. The results showed that a 42% degradation of the endothelial glycocalyx by HAase treatment increased Vw, LDL coverage, and MMID. Shear stress increased Vw, which cannot be inhibited by HAase treatment. Four hour-shear application increased about fourfolds of LDL coverage, whereas exerted no significant effects on its MMID, EC apoptosis, and the leaky junctions. On the contrary, 24-h shear exposure has no significant effects on LDL coverage, whereas increased 2.74-folds of MMID and about 53% of EC apoptotic rates that could be inhibited by HAase treatment. These results suggest endothelial glycocalyx acts as a transport barrier by decreasing water and LDL transport, as well as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport into the vessel wall.NEW & NOTEWORTHY A 42% degradation of the endothelial glycocalyx by hyaluronidase of the isolated rat abdominal aorta facilitated water and LDL transport across the vessel wall, suggesting endothelial glycocalyx as a transport barrier. A 24-h shear exposure increased LDL mean maximum infiltration distance, and enhanced EC apoptosis, which could be both inhibited by hyaluronidase treatment, suggesting endothelial glycocalyx may also act as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport.
Keywords: EC apoptosis; LDL transport; endothelial glycocalyx; leaky junctions; transmural water flux.