Abstract Number: PB1269
Meeting: ISTH 2022 Congress
Background: The glycocalyx is a layer of sugars on endothelial cells (EC) enriched in heparan sulfate (HS). During inflammation, alteration in sulfation and shedding of HS occurs, activating both pro-inflammatory and pro-coagulant pathways. Arterial and venous EC respond differently to inflammatory cues, but whether this is due to distinct glycocalyx/HS dynamics is not known.
Aims: Here we investigate differences in sulfation and/or shedding of HS between arterial and venous cells in response to inflammatory stimuli.
Methods: Isolated porcine arterial and venous EC were cultured under static, high (typical for arteries) or low (typical for veins) shear stress using a 3D microfluidic system. HS expression and -shedding were detected using immunofluorescence. Sulfation was indirectly determined by quantitation of Ndst1 transcripts, encoding a HS-sulfotransferase. Next, shedding of HS was quantified after EC activation with human serum, tumor necrosis factor alpha (TNF𝛼) or lipopolysaccharide (LPS).
Results: HS was detected on arterial cells exclusively under flow, while it was observed on venous cells in both static and flow conditions, indicating that glycocalyx dynamics differ between these cells. Assessment of shear stress revealed that non-physiological shear stress impacts Ndst1 expression, causing an increase of sulfation in arterial cells (low shear) and a decrease in venous cells (high shear), without impact on the overall HS expression. Next, glycocalyx was detected upon EC activation. Surprisingly, no HS shedding from venous cells was observed when activated with human serum, TNF𝛼 or LPS whereas HS was shed from arterial EC.
Conclusion(s): The different glycocalyx response upon shear stress and activation suggests that physiological shear is essential to maintain normal HS sulfation levels and indicates that the glycocalyx on venous but not arterial cells is resistant to shedding upon inflammation. This could account for the diverse behavior of venous and arterial cells during inflammatory events.
To cite this abstract in AMA style:Milusev A, Rieben R, Sorvillo N. Inflammatory stimuli reveal a differential glycocalyx response between venous and arterial endothelial cells [abstract]. https://abstracts.isth.org/abstract/inflammatory-stimuli-reveal-a-differential-glycocalyx-response-between-venous-and-arterial-endothelial-cells/. Accessed October 1, 2023.
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