Compositional or charge density modification of the endothelial glycocalyx accelerates flow-dependent concentration...

We hypothesized that diminished endothelial glycocalyx (GCX) at atherosclerotic lesion-prone sites accelerates flow-dependent concentration polarization of low-density lipoproteins (LDLs) at the luminal surface, and in turn contributes to vulnerability of these sites to atherosclerosis. A parallel plate flow chamber was applied to expose cultured endothelial monolayers to three different levels of shear stress (3, 12, 20 dyn/cm(2)). Heparinase III (Hep.III) was employed to degrade heparan sulfate proteoglycans selectively and 3-(N-morpholino) propanesulfonic acid-buffered physiological salt solutions (MOPS-PSS) were used at either normal ionic strength (Normal-MOPS), low ionic strength (LO-MOPS) or high ionic strength (HI-MOPS) to modify the effective charge density of the endothelial GCX. Water filtration velocity (V(w)) across the endothelial monolayer, the luminal concentration of LDLs (C(w)) and the uptake of LDLs by endothelial cells were measured and compared among the following five groups of cells: (1) Control; (2) Hep.III treatment; (3) LO-MOPS; (4) Normal-MOPS; and (5) HI-MOPS. The results obtained substantiated the aforementioned hypothesis and demonstrated that compositional or charge density modification of the endothelial GCX facilitated water filtration across the endothelium, enhanced the accumulation of LDLs on the luminal surface and increased the uptake of LDLs by endothelial cells, therefore contributing to atherogenesis.