Impaired glycocalyx barrier properties contribute to enhanced intimal low-density lipoprotein accumulation at the carotid artery bifurcation in mice

The glycocalyx contributes to the barrier properties of vascular endothelium, and recently, we reported using electron microscopy that glycocalyx is diminished at lesion prone sites in arterial bifurcations in mice. In the present study, we examined using confocal microscopy the dimension and composition of the endothelial glycocalyx at low- and high-risk atherogenic regions within the common carotid (common) and internal carotid branch (sinus) of C57BL/6J mice and compared dimensional variations with its ability to limit transendothelial leakage of low-density lipoprotein (LDL). Confocal laser scanning microscopy of arterial surfaces stained for heparan sulfate and hyaluronan revealed thinner glycocalyces at the sinus region (2.2 +/- 0.7 and 2.3 +/- 0.7 mu m, respectively; P < 0.05) than the glycocalyx thickness at the common region (4.3 +/- 1.6 and 4.3 +/- 1.6 mu m, respectively). This thinner glycocalyx was associated with impaired LDL retention by the glycocalyx resulting in a two to three times increase in intimal accumulation of LDL 15 min after i.v. bolus administration: 10.8 +/- 5.6 vs. 4.0 +/- 1.9 x 10,000 a.u. (sinus vs. common, P < 0.05). These results indicate that impaired glycocalyx barrier properties may contribute to transendothelial leakage of atherogenic LDL at lesion prone arterial sites.