High glucose-mediated loss of cell surface heparan sulfate proteoglycan impairs the endothelial shear stress response

Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Elevated glucose concentrations have been shown to impair this response, though the precise mechanism of damage is not clear. Using an in vitro model of hyperglycemia, we tested the hypothesis that high glucose (HG) impairs the endothelial shear stress response by damaging the glycocalyx. 50 mU/mL heparinase III enzyme removes similar proportions of cell surface heparan sulfate proteoglycan (HSPG) as HG conditions and results in similar impairment of the elongation and alignment response to flow. Doubling the shear stress overcomes the inhibited flow response in HG cells, but not in enzyme treated cells. These findings may be explained by HG leading to decreased expression of full-length HSPG; whereas, heparinase results in a normal density of HSPG of shorter length.