AMP dependent protein kinase regulates endothelial heparan sulfate expression in response to an inflammatory stimulus under arterial shear stress.

Heparan sulfate (HS) is the most abundant glycosaminoglycan on the vascular endothelium and can regulate endothelial cell morphology and function in response to mechanical stimuli. This study investigated endothelial HS response to an inflammatory stimulus under static and arterial shear stress conditions. Human aortic endothelial cells (HAECs) under static conditions expressed significantly higher HS when treated with an inflammatory stimulus compared to untreated controls. HAECs exposed to an inflammatory stimulus after being conditioned with 10 dyn/cm(2) of shear stress for 24 h did not express significantly higher HS compared to untreated controls under flow. To investigate the mechanism underlying this differential endothelial HS expression in response to an inflammatory stimulus under static and shear stress conditions, we hypothesized a shear dependent increase in AMP dependent protein kinase (AMPK) was regulating HS response to the inflammatory stimulus. AMPK inhibition using compound C decreased HAEC HS expression in response to inflammatory stimulus under arterial shear stress, revealing AMPK as a regulator of HS expression. Further investigation is needed to elucidate the mechanistic pathways underlying the interactions between HS and AMPK expression in endothelial cells and how they regulate HAEC inflammatory response.