Objective

The long saphenous vein is the most used commonly conduit in cardiac surgery; however, its use is complicated by late vein graft failure due to the development of vascular inflammation and intimal hyperplasia. Acute changes in haemodynamic forces (mainly shear stress) have been implicated in the initiation of vascular inflammation, however the exact mechanisms are still not fully understood. We aim to investigate the role of acute shear stress on the activation of NF-κB signalling pathway.

Methods

Human Umbilical Vein Endothelial Cells (HUVECs) were cultured under static condition or exposed to acute high shear stress (12 dyn/cm²) for various time points. NF-κB activation was assessed at 30 and 90 minutes using Immunofluorescence and western blotting. Inflammatory gene expression was investigated at 90, 120 and 240 minutes respectively using qPCR.

Results

The exposure of cells to acute shear stress for 30 and 90min resulted in significant nuclear translocation of NF-κB in cells cultured under shear compared to static (p<0.01 and p<0.05, respectively) which was associated with significant IkBα degradation (p<0.01) and the upregulation of pro-inflammatory genes expression such as MCP-1 and IL-6 (p<0.05). The use of IKKβ specific inhibitor resulted in significant inhibition of pro-inflammatory genes expression (p<0.05) in response to shear stress.

Conclusion

Acute shear stress leads to the activation of NF-κB canonical pathway and the upregulation of pro-inflammatory genes. Inhibition of the canonical pathway can diminish pro-inflammatory responses and may provide a novel pre-treatment option for vein graft failure.